TY  - JOUR
AU  - Jadranin, Milka
AU  - Savić, Danica
AU  - Lupšić, Ema
AU  - Podolski-Renić, Ana
AU  - Pešić, Milica
AU  - Tešević, Vele
AU  - Milosavljević, Slobodan M.
AU  - Krstić, Gordana B.
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/7540
AB  - Euphorbia seguieriana ssp. seguieriana Necker (ES) and Euphorbia cyparissias (EC) with a habitat in the Deliblato Sands were the subject of this examination. The latexes of these so far insufficiently investigated species of the Euphorbia genus are used in traditional medicine for the treatment of wounds and warts on the skin. To determine their chemical composition, non-targeted screening of the latexes’ chloroform extracts was performed using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry employing an electrospray ionization source (LC-ESI QTOF MS). The analysis of the obtained results showed that the latexes of ES and EC represent rich sources of diterpenes, tentatively identified as jatrophanes, ingenanes, tiglianes, myrsinanes, premyrsinanes, and others. Examination of the anticancer activity of the ES and EC latex extracts showed that both extracts significantly inhibited the growth of the non-small cell lung carcinoma NCI-H460 and glioblastoma U87 cell lines as well as of their corresponding multi-drug resistant (MDR) cell lines, NCI-H460/R and U87-TxR. The obtained results also revealed that the ES and EC extracts inhibited the function of P-glycoprotein (P-gp) in MDR cancer cells, whose overexpression is one of the main mechanisms underlying MDR.
PB  - MDPI
T2  - Plants
T1  - LC-ESI QToF MS Non-Targeted Screening of Latex Extracts of Euphorbia seguieriana ssp. seguieriana Necker and Euphorbia cyparissias and Determination of Their Potential Anticancer Activity
VL  - 12
IS  - 24
SP  - 4181
DO  - 10.3390/plants12244181
ER  - 

@article{
author = "Jadranin, Milka and Savić, Danica and Lupšić, Ema and Podolski-Renić, Ana and Pešić, Milica and Tešević, Vele and Milosavljević, Slobodan M. and Krstić, Gordana B.",
year = "2023",
abstract = "Euphorbia seguieriana ssp. seguieriana Necker (ES) and Euphorbia cyparissias (EC) with a habitat in the Deliblato Sands were the subject of this examination. The latexes of these so far insufficiently investigated species of the Euphorbia genus are used in traditional medicine for the treatment of wounds and warts on the skin. To determine their chemical composition, non-targeted screening of the latexes’ chloroform extracts was performed using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry employing an electrospray ionization source (LC-ESI QTOF MS). The analysis of the obtained results showed that the latexes of ES and EC represent rich sources of diterpenes, tentatively identified as jatrophanes, ingenanes, tiglianes, myrsinanes, premyrsinanes, and others. Examination of the anticancer activity of the ES and EC latex extracts showed that both extracts significantly inhibited the growth of the non-small cell lung carcinoma NCI-H460 and glioblastoma U87 cell lines as well as of their corresponding multi-drug resistant (MDR) cell lines, NCI-H460/R and U87-TxR. The obtained results also revealed that the ES and EC extracts inhibited the function of P-glycoprotein (P-gp) in MDR cancer cells, whose overexpression is one of the main mechanisms underlying MDR.",
publisher = "MDPI",
journal = "Plants",
title = "LC-ESI QToF MS Non-Targeted Screening of Latex Extracts of Euphorbia seguieriana ssp. seguieriana Necker and Euphorbia cyparissias and Determination of Their Potential Anticancer Activity",
volume = "12",
number = "24",
pages = "4181",
doi = "10.3390/plants12244181"
}

Jadranin, M., Savić, D., Lupšić, E., Podolski-Renić, A., Pešić, M., Tešević, V., Milosavljević, S. M.,& Krstić, G. B.. (2023). LC-ESI QToF MS Non-Targeted Screening of Latex Extracts of Euphorbia seguieriana ssp. seguieriana Necker and Euphorbia cyparissias and Determination of Their Potential Anticancer Activity. in Plants
MDPI., 12(24), 4181.
https://doi.org/10.3390/plants12244181

Jadranin M, Savić D, Lupšić E, Podolski-Renić A, Pešić M, Tešević V, Milosavljević SM, Krstić GB. LC-ESI QToF MS Non-Targeted Screening of Latex Extracts of Euphorbia seguieriana ssp. seguieriana Necker and Euphorbia cyparissias and Determination of Their Potential Anticancer Activity. in Plants. 2023;12(24):4181.
doi:10.3390/plants12244181 .

Jadranin, Milka, Savić, Danica, Lupšić, Ema, Podolski-Renić, Ana, Pešić, Milica, Tešević, Vele, Milosavljević, Slobodan M., Krstić, Gordana B., "LC-ESI QToF MS Non-Targeted Screening of Latex Extracts of Euphorbia seguieriana ssp. seguieriana Necker and Euphorbia cyparissias and Determination of Their Potential Anticancer Activity" in Plants, 12, no. 24 (2023):4181,
https://doi.org/10.3390/plants12244181 . .

TY  - CONF
AU  - Stepanović, Ana
AU  - Lupšić, Ema
AU  - Dinić, Jelena
AU  - Podolski-Renić, Ana
AU  - Pajović, Milica
AU  - Jovanović Stojanov, Sofija
AU  - Dragoj, Miodrag
AU  - Terzić Jovanović, Nataša
AU  - Opsenica, Igor
AU  - Pešić, Milica
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/6678
AB  - Background: Doxorubicin (DOX) has been very effective against glioblastoma invitro. Its application in vivo is hampered because it cannot pass the blood–brainbarrier (BBB). Significant research efforts are invested to overcome this limitation.Sclareol (SC) is an aromatic compound naturally found in clary sage. Thecombination of SC and DOX showed promising effects in different tumor types invitro and in vivo. Therefore, we tested their combination and innovative hybridmolecules (SC:DOX) on glioblastoma cells with the expression of P-glycoprotein, amajor component of BBB and cancer multidrug resistance marker. Methods:Cytotoxicity and selectivity towards glioblastoma cells of SC, DOX, theircombination, and SC:DOX were examined by MTT assay. The effect of SC on DOXaccumulation was determined by flow cytometry. We also studied SC:DOXaccumulation, cellular uptake, localization imaging, and DNA damage induction.Results: The effects of simultaneous SC and DOX treatments demonstrated theconsiderable potential of SC to reverse DOX resistance in glioblastoma cells andincrease DOX accumulation. SC:DOX hybrids, named CON1 and CON2 were lesscytotoxic than DOX, but with reduced resistance and increased selectivity towardsglioblastoma cells. Cellular uptake of CON1 and CON2 was increased in glioblastomacells compared to DOX. Perinuclear localization of CON1 and CON2 vs. nuclearlocalization of DOX as well as no DNA damaging effects suggest a differentmechanism of action for SC:DOX. Conclusion: The combination of SC and DOX, andtheir innovative hybrids, could be considered a promising strategy that can overcomethe limitations of DOX application in glioblastoma.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of abstracts - 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - New anti-glioblastoma strategy with natural compounds sclareol and doxorubicin
SP  - 71
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5905
ER  - 

@conference{
author = "Stepanović, Ana and Lupšić, Ema and Dinić, Jelena and Podolski-Renić, Ana and Pajović, Milica and Jovanović Stojanov, Sofija and Dragoj, Miodrag and Terzić Jovanović, Nataša and Opsenica, Igor and Pešić, Milica",
year = "2023",
abstract = "Background: Doxorubicin (DOX) has been very effective against glioblastoma invitro. Its application in vivo is hampered because it cannot pass the blood–brainbarrier (BBB). Significant research efforts are invested to overcome this limitation.Sclareol (SC) is an aromatic compound naturally found in clary sage. Thecombination of SC and DOX showed promising effects in different tumor types invitro and in vivo. Therefore, we tested their combination and innovative hybridmolecules (SC:DOX) on glioblastoma cells with the expression of P-glycoprotein, amajor component of BBB and cancer multidrug resistance marker. Methods:Cytotoxicity and selectivity towards glioblastoma cells of SC, DOX, theircombination, and SC:DOX were examined by MTT assay. The effect of SC on DOXaccumulation was determined by flow cytometry. We also studied SC:DOXaccumulation, cellular uptake, localization imaging, and DNA damage induction.Results: The effects of simultaneous SC and DOX treatments demonstrated theconsiderable potential of SC to reverse DOX resistance in glioblastoma cells andincrease DOX accumulation. SC:DOX hybrids, named CON1 and CON2 were lesscytotoxic than DOX, but with reduced resistance and increased selectivity towardsglioblastoma cells. Cellular uptake of CON1 and CON2 was increased in glioblastomacells compared to DOX. Perinuclear localization of CON1 and CON2 vs. nuclearlocalization of DOX as well as no DNA damaging effects suggest a differentmechanism of action for SC:DOX. Conclusion: The combination of SC and DOX, andtheir innovative hybrids, could be considered a promising strategy that can overcomethe limitations of DOX application in glioblastoma.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of abstracts - 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "New anti-glioblastoma strategy with natural compounds sclareol and doxorubicin",
pages = "71",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5905"
}

Stepanović, A., Lupšić, E., Dinić, J., Podolski-Renić, A., Pajović, M., Jovanović Stojanov, S., Dragoj, M., Terzić Jovanović, N., Opsenica, I.,& Pešić, M.. (2023). New anti-glioblastoma strategy with natural compounds sclareol and doxorubicin. in Book of abstracts - 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 71.
https://hdl.handle.net/21.15107/rcub_ibiss_5905

Stepanović A, Lupšić E, Dinić J, Podolski-Renić A, Pajović M, Jovanović Stojanov S, Dragoj M, Terzić Jovanović N, Opsenica I, Pešić M. New anti-glioblastoma strategy with natural compounds sclareol and doxorubicin. in Book of abstracts - 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:71.
https://hdl.handle.net/21.15107/rcub_ibiss_5905 .

Stepanović, Ana, Lupšić, Ema, Dinić, Jelena, Podolski-Renić, Ana, Pajović, Milica, Jovanović Stojanov, Sofija, Dragoj, Miodrag, Terzić Jovanović, Nataša, Opsenica, Igor, Pešić, Milica, "New anti-glioblastoma strategy with natural compounds sclareol and doxorubicin" in Book of abstracts - 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):71,
https://hdl.handle.net/21.15107/rcub_ibiss_5905 .

TY  - CONF
AU  - Jadranin, Milka
AU  - Krstić, Gordana
AU  - Savić, Danica
AU  - Novaković, Miroslav
AU  - Lekić, Stefan
AU  - Tešević, Vele
AU  - Pešić, Milica
AU  - Podolski-Renić, Ana
AU  - Lupšić, Ema
AU  - Milosavljević, Slobodan
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/7270
AB  - Euphorbia cyparissias L. (cypress spurge) is one of the many species of the genus Euphorbia. Like other plant species of the genus, E. cyparissias is a source of biologically active compounds [1, 2]. The aim of this research was to profile the chloroform-methanol latex extract and detect the type of secondary metabolites of Serbian E. cyparissias, collected in Deliblato Sand 
(Serbia) in May 2022, using liquid chromatography – electrospray ionisation mass spectrometry. Based on the obtained results, terpene derivatives have been found as the most abundant in the latex extract, mainly diterpenes (jatrophanes and ingenanes) and triterpenes. Also, the anticancer activ ity of the latex extract on the cell lines NCI-H460, NCI-H460/R, U87, U87/
TxR and MRC-5, as well as the ability to inhibit P-gp, were examined. Latex extract exhibited anticancer activity against all tested cell lines, and also 
proved to be a strong P-gp inhibitor. The obtained results are in accordance with the literature data because jatrophanes are well-known strong P-gp 
inhibitors [3]. These preliminary results indicate that this plant material is a rich source of biologically active compounds and detailed phytochemical research of E. cyparissias is further planned.
PB  - International Conference on Natural Products Utilization - ICNPU2023
C3  - Book of Abstracts - The 5th International Conference on Natural Products Utilization: from Plants to Pharmacy Shelf (ICNPU-2023), 30 May–02 June 2023, Sts. Constantine and Helena - Varna, Bulgaria
T1  - Analysis of terpenoids from the latex of Euphorbia cyparissias by liquid chromatography-electrospray ionization mass spectrometry
SP  - 184
EP  - 185
UR  - https://hdl.handle.net/21.15107/rcub_cer_7270
ER  - 

@conference{
author = "Jadranin, Milka and Krstić, Gordana and Savić, Danica and Novaković, Miroslav and Lekić, Stefan and Tešević, Vele and Pešić, Milica and Podolski-Renić, Ana and Lupšić, Ema and Milosavljević, Slobodan",
year = "2023",
abstract = "Euphorbia cyparissias L. (cypress spurge) is one of the many species of the genus Euphorbia. Like other plant species of the genus, E. cyparissias is a source of biologically active compounds [1, 2]. The aim of this research was to profile the chloroform-methanol latex extract and detect the type of secondary metabolites of Serbian E. cyparissias, collected in Deliblato Sand 
(Serbia) in May 2022, using liquid chromatography – electrospray ionisation mass spectrometry. Based on the obtained results, terpene derivatives have been found as the most abundant in the latex extract, mainly diterpenes (jatrophanes and ingenanes) and triterpenes. Also, the anticancer activ ity of the latex extract on the cell lines NCI-H460, NCI-H460/R, U87, U87/
TxR and MRC-5, as well as the ability to inhibit P-gp, were examined. Latex extract exhibited anticancer activity against all tested cell lines, and also 
proved to be a strong P-gp inhibitor. The obtained results are in accordance with the literature data because jatrophanes are well-known strong P-gp 
inhibitors [3]. These preliminary results indicate that this plant material is a rich source of biologically active compounds and detailed phytochemical research of E. cyparissias is further planned.",
publisher = "International Conference on Natural Products Utilization - ICNPU2023",
journal = "Book of Abstracts - The 5th International Conference on Natural Products Utilization: from Plants to Pharmacy Shelf (ICNPU-2023), 30 May–02 June 2023, Sts. Constantine and Helena - Varna, Bulgaria",
title = "Analysis of terpenoids from the latex of Euphorbia cyparissias by liquid chromatography-electrospray ionization mass spectrometry",
pages = "184-185",
url = "https://hdl.handle.net/21.15107/rcub_cer_7270"
}

Jadranin, M., Krstić, G., Savić, D., Novaković, M., Lekić, S., Tešević, V., Pešić, M., Podolski-Renić, A., Lupšić, E.,& Milosavljević, S.. (2023). Analysis of terpenoids from the latex of Euphorbia cyparissias by liquid chromatography-electrospray ionization mass spectrometry. in Book of Abstracts - The 5th International Conference on Natural Products Utilization: from Plants to Pharmacy Shelf (ICNPU-2023), 30 May–02 June 2023, Sts. Constantine and Helena - Varna, Bulgaria
International Conference on Natural Products Utilization - ICNPU2023., 184-185.
https://hdl.handle.net/21.15107/rcub_cer_7270

Jadranin M, Krstić G, Savić D, Novaković M, Lekić S, Tešević V, Pešić M, Podolski-Renić A, Lupšić E, Milosavljević S. Analysis of terpenoids from the latex of Euphorbia cyparissias by liquid chromatography-electrospray ionization mass spectrometry. in Book of Abstracts - The 5th International Conference on Natural Products Utilization: from Plants to Pharmacy Shelf (ICNPU-2023), 30 May–02 June 2023, Sts. Constantine and Helena - Varna, Bulgaria. 2023;:184-185.
https://hdl.handle.net/21.15107/rcub_cer_7270 .

Jadranin, Milka, Krstić, Gordana, Savić, Danica, Novaković, Miroslav, Lekić, Stefan, Tešević, Vele, Pešić, Milica, Podolski-Renić, Ana, Lupšić, Ema, Milosavljević, Slobodan, "Analysis of terpenoids from the latex of Euphorbia cyparissias by liquid chromatography-electrospray ionization mass spectrometry" in Book of Abstracts - The 5th International Conference on Natural Products Utilization: from Plants to Pharmacy Shelf (ICNPU-2023), 30 May–02 June 2023, Sts. Constantine and Helena - Varna, Bulgaria (2023):184-185,
https://hdl.handle.net/21.15107/rcub_cer_7270 .

TY  - JOUR
AU  - Stojković, Pavle
AU  - Kostić, Ana
AU  - Lupšić, Ema
AU  - Terzić-Jovanović, Nataša
AU  - Novaković, Miroslav
AU  - Nedialkov, Paraskev
AU  - Trendafilova, Antoaneta
AU  - Pešić, Milica
AU  - Opsenica, Igor
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/7183
AB  - The synthesis of 24 hybrid molecules, consisting of naturally occurring sclareol (SCL) and synthetic 1,2,4-triazolo[1,5-a]pyrimidines (TPs), is described. New compounds were designed with the aim of improving the cytotoxic properties, activity, and selectivity of the parent compounds. Six analogs (12a-f) contained 4-benzylpiperazine linkage, while 4-benzyldiamine linkage was present in eighteen derivatives (12g-r and 13a-f). Hybrids 13a-f consist of two TP units. After purification, all hybrids (12a-r and 13a-f), as well as their precursors (9a-e and 11a-c), were tested on human glioblastoma U87 cells. More than half of the tested synthesized molecules, 16 out of 31, caused a significant reduction of U87 cell viability (more than 75% reduction) at 30 µM. The concentration-dependent cytotoxicity of these 16 compounds was also examined on U87 cells, corresponding multidrug-resistant (MDR) U87-TxR cells with increased P-glycoprotein (P-gp) expression and activity, and normal lung fibroblasts MRC-5. Importantly, 12l and 12r were active in the nanomolar range, while seven compounds (11b, 11c, 12i, 12l, 12n, 12q, and 12r) were more selective towards glioblastoma cells than SCL. All compounds except 12r evaded MDR, showing even better cytotoxicity in U87-TxR cells. In particular, 11c, 12a, 12g, 12j, 12k, 12m, 12n, and SCL showed collateral sensitivity. Hybrid compounds 12l, 12q, and 12r decreased P-gp activity to the same extent as a well-known P-gp inhibitor - tariquidar (TQ). Hybrid compound 12l and its precursor 11c affected different cellular processes including the cell cycle, cell death, and mitochondrial membrane potential, and changed the levels of reactive oxygen and nitrogen species (ROS/RNS) in glioblastoma cells. Collateral sensitivity towards MDR glioblastoma cells was caused by the modulation of oxidative stress accompanied by inhibition of mitochondria.
PB  - Elsevier
T2  - Bioorganic Chemistry
T1  - Novel hybrids of sclareol and 1,2,4-triazolo[1,5-a]pyrimidine show collateral sensitivity in multidrug-resistant glioblastoma cells
VL  - 138
SP  - 106605
DO  - 10.1016/j.bioorg.2023.106605
ER  - 

@article{
author = "Stojković, Pavle and Kostić, Ana and Lupšić, Ema and Terzić-Jovanović, Nataša and Novaković, Miroslav and Nedialkov, Paraskev and Trendafilova, Antoaneta and Pešić, Milica and Opsenica, Igor",
year = "2023",
abstract = "The synthesis of 24 hybrid molecules, consisting of naturally occurring sclareol (SCL) and synthetic 1,2,4-triazolo[1,5-a]pyrimidines (TPs), is described. New compounds were designed with the aim of improving the cytotoxic properties, activity, and selectivity of the parent compounds. Six analogs (12a-f) contained 4-benzylpiperazine linkage, while 4-benzyldiamine linkage was present in eighteen derivatives (12g-r and 13a-f). Hybrids 13a-f consist of two TP units. After purification, all hybrids (12a-r and 13a-f), as well as their precursors (9a-e and 11a-c), were tested on human glioblastoma U87 cells. More than half of the tested synthesized molecules, 16 out of 31, caused a significant reduction of U87 cell viability (more than 75% reduction) at 30 µM. The concentration-dependent cytotoxicity of these 16 compounds was also examined on U87 cells, corresponding multidrug-resistant (MDR) U87-TxR cells with increased P-glycoprotein (P-gp) expression and activity, and normal lung fibroblasts MRC-5. Importantly, 12l and 12r were active in the nanomolar range, while seven compounds (11b, 11c, 12i, 12l, 12n, 12q, and 12r) were more selective towards glioblastoma cells than SCL. All compounds except 12r evaded MDR, showing even better cytotoxicity in U87-TxR cells. In particular, 11c, 12a, 12g, 12j, 12k, 12m, 12n, and SCL showed collateral sensitivity. Hybrid compounds 12l, 12q, and 12r decreased P-gp activity to the same extent as a well-known P-gp inhibitor - tariquidar (TQ). Hybrid compound 12l and its precursor 11c affected different cellular processes including the cell cycle, cell death, and mitochondrial membrane potential, and changed the levels of reactive oxygen and nitrogen species (ROS/RNS) in glioblastoma cells. Collateral sensitivity towards MDR glioblastoma cells was caused by the modulation of oxidative stress accompanied by inhibition of mitochondria.",
publisher = "Elsevier",
journal = "Bioorganic Chemistry",
title = "Novel hybrids of sclareol and 1,2,4-triazolo[1,5-a]pyrimidine show collateral sensitivity in multidrug-resistant glioblastoma cells",
volume = "138",
pages = "106605",
doi = "10.1016/j.bioorg.2023.106605"
}

Stojković, P., Kostić, A., Lupšić, E., Terzić-Jovanović, N., Novaković, M., Nedialkov, P., Trendafilova, A., Pešić, M.,& Opsenica, I.. (2023). Novel hybrids of sclareol and 1,2,4-triazolo[1,5-a]pyrimidine show collateral sensitivity in multidrug-resistant glioblastoma cells. in Bioorganic Chemistry
Elsevier., 138, 106605.
https://doi.org/10.1016/j.bioorg.2023.106605

Stojković P, Kostić A, Lupšić E, Terzić-Jovanović N, Novaković M, Nedialkov P, Trendafilova A, Pešić M, Opsenica I. Novel hybrids of sclareol and 1,2,4-triazolo[1,5-a]pyrimidine show collateral sensitivity in multidrug-resistant glioblastoma cells. in Bioorganic Chemistry. 2023;138:106605.
doi:10.1016/j.bioorg.2023.106605 .

Stojković, Pavle, Kostić, Ana, Lupšić, Ema, Terzić-Jovanović, Nataša, Novaković, Miroslav, Nedialkov, Paraskev, Trendafilova, Antoaneta, Pešić, Milica, Opsenica, Igor, "Novel hybrids of sclareol and 1,2,4-triazolo[1,5-a]pyrimidine show collateral sensitivity in multidrug-resistant glioblastoma cells" in Bioorganic Chemistry, 138 (2023):106605,
https://doi.org/10.1016/j.bioorg.2023.106605 . .

TY  - JOUR
AU  - Koračak, Ljiljana
AU  - Lupšić, Ema
AU  - Terzić-Jovanović, Nataša
AU  - Jovanović, Mirna
AU  - Novaković, Miroslav
AU  - Nedialkov, Paraskev
AU  - Trendafilova, Antoaneta
AU  - Zlatović, Mario
AU  - Pešić, Milica
AU  - Opsenica, Igor
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/7172
AB  - The synthesis of 17 hybrid molecules, consisting of artesunate, a derivative of naturally occurring artemisinin, and synthetic 4-aryl-2-aminopyrimidines, is described. New compounds were designed to improve the parent compounds' cytotoxic properties, activity, and selectivity. The synthesized hybrid molecules (15a–f with ethylenediamine linker and 16a–k with piperazine linker), as well as their precursors – pyrimidine derivatives (13a–f and 14a–k), artemisinin, and artesunate, were tested on sensitive and multidrug-resistant (MDR) human non-small cell lung carcinoma (NSCLC) cells. All hybrid compounds with piperazine linker 16a–k were selective toward NSCLC cells and displayed IC50 values below 5 μM. Although they showed similar anticancer potency as artesunate, their selectivity against cancer cells was considerably improved. Importantly, 16h–k hybrid compounds were able to evade MDR phenotype, inhibit P-glycoprotein (P-gp) activity, and increase the sensitivity of MDR NSCLC cells to doxorubicin (DOX). The inhibition of P-gp activity induced by 16h–j was stronger than the one obtained with artesunate. Among these four hybrid compounds, 16k was the most potent anticancer agent with similar IC50 values of around 1.5 μM (for comparison – over 3.1 μM for artesunate) in sensitive and MDR NSCLC cells.
PB  - Royal Society of Chemistry
T2  - New Journal of Chemistry
T1  - Novel artesunate–pyrimidine-based hybrids with anticancer potential against multidrug-resistant cancer cells
VL  - 47
IS  - 14
SP  - 6844
EP  - 6855
DO  - 10.1039/D3NJ00427A
ER  - 

@article{
author = "Koračak, Ljiljana and Lupšić, Ema and Terzić-Jovanović, Nataša and Jovanović, Mirna and Novaković, Miroslav and Nedialkov, Paraskev and Trendafilova, Antoaneta and Zlatović, Mario and Pešić, Milica and Opsenica, Igor",
year = "2023",
abstract = "The synthesis of 17 hybrid molecules, consisting of artesunate, a derivative of naturally occurring artemisinin, and synthetic 4-aryl-2-aminopyrimidines, is described. New compounds were designed to improve the parent compounds' cytotoxic properties, activity, and selectivity. The synthesized hybrid molecules (15a–f with ethylenediamine linker and 16a–k with piperazine linker), as well as their precursors – pyrimidine derivatives (13a–f and 14a–k), artemisinin, and artesunate, were tested on sensitive and multidrug-resistant (MDR) human non-small cell lung carcinoma (NSCLC) cells. All hybrid compounds with piperazine linker 16a–k were selective toward NSCLC cells and displayed IC50 values below 5 μM. Although they showed similar anticancer potency as artesunate, their selectivity against cancer cells was considerably improved. Importantly, 16h–k hybrid compounds were able to evade MDR phenotype, inhibit P-glycoprotein (P-gp) activity, and increase the sensitivity of MDR NSCLC cells to doxorubicin (DOX). The inhibition of P-gp activity induced by 16h–j was stronger than the one obtained with artesunate. Among these four hybrid compounds, 16k was the most potent anticancer agent with similar IC50 values of around 1.5 μM (for comparison – over 3.1 μM for artesunate) in sensitive and MDR NSCLC cells.",
publisher = "Royal Society of Chemistry",
journal = "New Journal of Chemistry",
title = "Novel artesunate–pyrimidine-based hybrids with anticancer potential against multidrug-resistant cancer cells",
volume = "47",
number = "14",
pages = "6844-6855",
doi = "10.1039/D3NJ00427A"
}

Koračak, L., Lupšić, E., Terzić-Jovanović, N., Jovanović, M., Novaković, M., Nedialkov, P., Trendafilova, A., Zlatović, M., Pešić, M.,& Opsenica, I.. (2023). Novel artesunate–pyrimidine-based hybrids with anticancer potential against multidrug-resistant cancer cells. in New Journal of Chemistry
Royal Society of Chemistry., 47(14), 6844-6855.
https://doi.org/10.1039/D3NJ00427A

Koračak L, Lupšić E, Terzić-Jovanović N, Jovanović M, Novaković M, Nedialkov P, Trendafilova A, Zlatović M, Pešić M, Opsenica I. Novel artesunate–pyrimidine-based hybrids with anticancer potential against multidrug-resistant cancer cells. in New Journal of Chemistry. 2023;47(14):6844-6855.
doi:10.1039/D3NJ00427A .

Koračak, Ljiljana, Lupšić, Ema, Terzić-Jovanović, Nataša, Jovanović, Mirna, Novaković, Miroslav, Nedialkov, Paraskev, Trendafilova, Antoaneta, Zlatović, Mario, Pešić, Milica, Opsenica, Igor, "Novel artesunate–pyrimidine-based hybrids with anticancer potential against multidrug-resistant cancer cells" in New Journal of Chemistry, 47, no. 14 (2023):6844-6855,
https://doi.org/10.1039/D3NJ00427A . .

TY  - CONF
AU  - Krstić, Gordana
AU  - Jadranin, Milka
AU  - Jovanović Stojanov, Sofija
AU  - Pešić, Milica
AU  - Tešević, Vele
AU  - Milosavljević, Slobodan
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5862
AB  - In this research, from two species, E. palustris and E.  lucida, four ingenane derivatives were isolated. Their anticancer effects were evaluated in the human melanoma  – 518A2 cell line and compared with the effects of ingenolmebutate. Selectivity towards human melanoma cells was  determined using normal human keratinocytes – HaCaT.
PB  - Macedonian Pharmaceutical Association
C3  - Macedonian Pharmaceutical Bulletin
T1  - Anti-melanoma effects of ingenanes isolated from Euphorbia species
VL  - 68
IS  - Suppl.2
SP  - 23
EP  - 24
DO  - 10.33320/maced.pharm.bull.2022.68.04.006
ER  - 

@conference{
author = "Krstić, Gordana and Jadranin, Milka and Jovanović Stojanov, Sofija and Pešić, Milica and Tešević, Vele and Milosavljević, Slobodan",
year = "2022",
abstract = "In this research, from two species, E. palustris and E.  lucida, four ingenane derivatives were isolated. Their anticancer effects were evaluated in the human melanoma  – 518A2 cell line and compared with the effects of ingenolmebutate. Selectivity towards human melanoma cells was  determined using normal human keratinocytes – HaCaT.",
publisher = "Macedonian Pharmaceutical Association",
journal = "Macedonian Pharmaceutical Bulletin",
title = "Anti-melanoma effects of ingenanes isolated from Euphorbia species",
volume = "68",
number = "Suppl.2",
pages = "23-24",
doi = "10.33320/maced.pharm.bull.2022.68.04.006"
}

Krstić, G., Jadranin, M., Jovanović Stojanov, S., Pešić, M., Tešević, V.,& Milosavljević, S.. (2022). Anti-melanoma effects of ingenanes isolated from Euphorbia species. in Macedonian Pharmaceutical Bulletin
Macedonian Pharmaceutical Association., 68(Suppl.2), 23-24.
https://doi.org/10.33320/maced.pharm.bull.2022.68.04.006

Krstić G, Jadranin M, Jovanović Stojanov S, Pešić M, Tešević V, Milosavljević S. Anti-melanoma effects of ingenanes isolated from Euphorbia species. in Macedonian Pharmaceutical Bulletin. 2022;68(Suppl.2):23-24.
doi:10.33320/maced.pharm.bull.2022.68.04.006 .

Krstić, Gordana, Jadranin, Milka, Jovanović Stojanov, Sofija, Pešić, Milica, Tešević, Vele, Milosavljević, Slobodan, "Anti-melanoma effects of ingenanes isolated from Euphorbia species" in Macedonian Pharmaceutical Bulletin, 68, no. Suppl.2 (2022):23-24,
https://doi.org/10.33320/maced.pharm.bull.2022.68.04.006 . .

TY  - JOUR
AU  - Krstić, Gordana
AU  - Kostić, Ana
AU  - Jadranin, Milka
AU  - Pešić, Milica
AU  - Novaković, Miroslav
AU  - Aljančić, Ivana
AU  - Vajs, Vlatka
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4910
AB  - In the previous study fifteen jatrophane diterpenes were isolated from the Euphorbia nicaeensis latex. Fourteen of them have been shown to be potent P-glycoprotein (P-gp) inhibitor in two MDR cancer cells (NCI-H460/R and DLD1-TxR). The aim of this study was to determine whether and which jatro­phane diterpenes can be isolated from the root of the plant, and then to examine their inhibition power on P-glycoprotein of selected cancer cell lines (NCI-H460, DLD1, U87, NCI-H460/R, DLD1-TxR and U87-TxR). Two previously undes­cribed jatrophane diterpenes were isolated from the root of E. nicaeensis col­lected in Deliblato Sand (Serbia). The structures of the isolated compounds were determined using 1D and 2D NMR, as well as HRESIMS data. The results obtained by MTT assay showed different antitumor potential of these two jatrophanes. Compound 1 inhibited cell growth of non-small cell lung car­cinoma cell lines NCI-H460 and NCI-H460/R, as well as glioblastoma cell lines U87 and U87-TxR, while jatrophane 2 was almost completely inactive in the suppression of cancer cell growth in a given range of concentrations. The obtained results also showed that the isolated compounds have an inhibitory effect on P-glycoprotein, as well as that their inhibitory potential is similar.
AB  - У претходном истраживању, петнаест дитерпена јатрофанског типа изоловано је из латекса Euphorbia nicaeensis. Њих четрнаест показала су се као снажни инхибитори P-гликопротеина (P-gp) у две MDR ћелијске линије рака (NCI-H460/R и DLD1-TxR). Циљ ове студије био је да се утврди да ли је и које јатрофанске дитерпене могуће изо- ловати из корена биљке, а затим испитивање њихове инхибиторне моћи на P-гликопро- теину одабраних ћелијских линија рака (NCI-H460, DLD1, U87, NCI-H460/R, DLD1-TxR и U87-TxR). Два претходно непозната јатрофана изолованa су из корена E. nicaeensis прикупљеног у Делиблатској пешчари. Структуре изолованих једињења одређене су применом 1D и 2D NMR метода, као и HRESIMS експеримента. Резултати добијени МТТ тестом показали су различит антиканцерогени потенцијал ова два јатрофана. Једињење 1 је инхибирало раст ћелија ћелијских линија неситноћелијског карцинома плућа NCI-H460 и NCI-H460/R, као и ћелијских линија глиобластома U87 и U87-TxR, док је јатрофан 2 био готово потпуно неефикасан у сузбијању растa ћелија карцинома у датом концентрационом опсегу. Добијени резултати су такође показали да 1 и 2 имају инхибиторно дејство на P-гликопротеин, као и да је њихов инхибиторни потенцијал сличан.
PB  - Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - Two new jatrophane diterpenes from the roots of Euphorbia nicaeensis
T1  - Два нова јатрофанска дитерпена из корена Euphorbia nicaeensis
IS  - 12
SP  - 1219
EP  - 1228
DO  - 10.2298/JSC210806085K
ER  - 

@article{
author = "Krstić, Gordana and Kostić, Ana and Jadranin, Milka and Pešić, Milica and Novaković, Miroslav and Aljančić, Ivana and Vajs, Vlatka",
year = "2021",
abstract = "In the previous study fifteen jatrophane diterpenes were isolated from the Euphorbia nicaeensis latex. Fourteen of them have been shown to be potent P-glycoprotein (P-gp) inhibitor in two MDR cancer cells (NCI-H460/R and DLD1-TxR). The aim of this study was to determine whether and which jatro­phane diterpenes can be isolated from the root of the plant, and then to examine their inhibition power on P-glycoprotein of selected cancer cell lines (NCI-H460, DLD1, U87, NCI-H460/R, DLD1-TxR and U87-TxR). Two previously undes­cribed jatrophane diterpenes were isolated from the root of E. nicaeensis col­lected in Deliblato Sand (Serbia). The structures of the isolated compounds were determined using 1D and 2D NMR, as well as HRESIMS data. The results obtained by MTT assay showed different antitumor potential of these two jatrophanes. Compound 1 inhibited cell growth of non-small cell lung car­cinoma cell lines NCI-H460 and NCI-H460/R, as well as glioblastoma cell lines U87 and U87-TxR, while jatrophane 2 was almost completely inactive in the suppression of cancer cell growth in a given range of concentrations. The obtained results also showed that the isolated compounds have an inhibitory effect on P-glycoprotein, as well as that their inhibitory potential is similar., У претходном истраживању, петнаест дитерпена јатрофанског типа изоловано је из латекса Euphorbia nicaeensis. Њих четрнаест показала су се као снажни инхибитори P-гликопротеина (P-gp) у две MDR ћелијске линије рака (NCI-H460/R и DLD1-TxR). Циљ ове студије био је да се утврди да ли је и које јатрофанске дитерпене могуће изо- ловати из корена биљке, а затим испитивање њихове инхибиторне моћи на P-гликопро- теину одабраних ћелијских линија рака (NCI-H460, DLD1, U87, NCI-H460/R, DLD1-TxR и U87-TxR). Два претходно непозната јатрофана изолованa су из корена E. nicaeensis прикупљеног у Делиблатској пешчари. Структуре изолованих једињења одређене су применом 1D и 2D NMR метода, као и HRESIMS експеримента. Резултати добијени МТТ тестом показали су различит антиканцерогени потенцијал ова два јатрофана. Једињење 1 је инхибирало раст ћелија ћелијских линија неситноћелијског карцинома плућа NCI-H460 и NCI-H460/R, као и ћелијских линија глиобластома U87 и U87-TxR, док је јатрофан 2 био готово потпуно неефикасан у сузбијању растa ћелија карцинома у датом концентрационом опсегу. Добијени резултати су такође показали да 1 и 2 имају инхибиторно дејство на P-гликопротеин, као и да је њихов инхибиторни потенцијал сличан.",
publisher = "Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "Two new jatrophane diterpenes from the roots of Euphorbia nicaeensis, Два нова јатрофанска дитерпена из корена Euphorbia nicaeensis",
number = "12",
pages = "1219-1228",
doi = "10.2298/JSC210806085K"
}

Krstić, G., Kostić, A., Jadranin, M., Pešić, M., Novaković, M., Aljančić, I.,& Vajs, V.. (2021). Two new jatrophane diterpenes from the roots of Euphorbia nicaeensis. in Journal of the Serbian Chemical Society
Serbian Chemical Society.(12), 1219-1228.
https://doi.org/10.2298/JSC210806085K

Krstić G, Kostić A, Jadranin M, Pešić M, Novaković M, Aljančić I, Vajs V. Two new jatrophane diterpenes from the roots of Euphorbia nicaeensis. in Journal of the Serbian Chemical Society. 2021;(12):1219-1228.
doi:10.2298/JSC210806085K .

Krstić, Gordana, Kostić, Ana, Jadranin, Milka, Pešić, Milica, Novaković, Miroslav, Aljančić, Ivana, Vajs, Vlatka, "Two new jatrophane diterpenes from the roots of Euphorbia nicaeensis" in Journal of the Serbian Chemical Society, no. 12 (2021):1219-1228,
https://doi.org/10.2298/JSC210806085K . .

TY  - CHAP
AU  - Dinić, Jelena
AU  - Novaković, Miroslav
AU  - Pešić, Milica
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4396
AB  - Natural products represent a key source of novel drug leads and their essential value in anticancer research is being increasingly recognized. The presence, quantity, and structural characteristics of natural compounds within the same species could differ between regions as a result of environmental variations contributing to intraspecific chemodiversity. The Balkan Peninsula is a vital part of Europe’s biodiversity, with a considerable number of endemic species and with a broad ecosystem distribution. This region provides an unlimited supply of unique, structurally diverse compounds and offers vast potential for discovering and developing therapeutics for human benefit. This chapter gives an overview of anticancer compounds derived from natural sources of the Balkans and underlines the importance for the long-term conservation of biodiversity in this part of Europe.
PB  - Elsevier
T2  - Biodiversity and Biomedicine: our future
T1  - Potential for cancer treatment: natural products from the Balkans
SP  - 137
EP  - 159
DO  - 10.1016/B978-0-12-819541-3.00009-8
ER  - 

@inbook{
author = "Dinić, Jelena and Novaković, Miroslav and Pešić, Milica",
year = "2020",
abstract = "Natural products represent a key source of novel drug leads and their essential value in anticancer research is being increasingly recognized. The presence, quantity, and structural characteristics of natural compounds within the same species could differ between regions as a result of environmental variations contributing to intraspecific chemodiversity. The Balkan Peninsula is a vital part of Europe’s biodiversity, with a considerable number of endemic species and with a broad ecosystem distribution. This region provides an unlimited supply of unique, structurally diverse compounds and offers vast potential for discovering and developing therapeutics for human benefit. This chapter gives an overview of anticancer compounds derived from natural sources of the Balkans and underlines the importance for the long-term conservation of biodiversity in this part of Europe.",
publisher = "Elsevier",
journal = "Biodiversity and Biomedicine: our future",
booktitle = "Potential for cancer treatment: natural products from the Balkans",
pages = "137-159",
doi = "10.1016/B978-0-12-819541-3.00009-8"
}

Dinić, J., Novaković, M.,& Pešić, M.. (2020). Potential for cancer treatment: natural products from the Balkans. in Biodiversity and Biomedicine: our future
Elsevier., 137-159.
https://doi.org/10.1016/B978-0-12-819541-3.00009-8

Dinić J, Novaković M, Pešić M. Potential for cancer treatment: natural products from the Balkans. in Biodiversity and Biomedicine: our future. 2020;:137-159.
doi:10.1016/B978-0-12-819541-3.00009-8 .

Dinić, Jelena, Novaković, Miroslav, Pešić, Milica, "Potential for cancer treatment: natural products from the Balkans" in Biodiversity and Biomedicine: our future (2020):137-159,
https://doi.org/10.1016/B978-0-12-819541-3.00009-8 . .

TY  - JOUR
AU  - Krstić, Gordana
AU  - Jadranin, Milka
AU  - Todorović, Nina
AU  - Pešić, Milica
AU  - Stankovic, Tijana
AU  - Aljančić, Ivana
AU  - Tešević, Vele
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2319
AB  - Seven previously undescribed jatrophane diterpenoids, nicaeenin A-G, with eight known jatrophane diterpenoids, namely euphodendrophanes A-C, F, N, O, Q S, were isolated from latex of Euphorbia nicaeensis collected in Serbia. The chemical structures of the compounds were determined by spectro-scopic analysis including 1D and 2D NMR and HRESIMS experiments. All but one of the previously undescribed jatrophanes, showed significant potential to inhibit P-glycoprotein (P-gp) activity in two MDR cancer cells (NCI-H460/12 and DLD1-TxR). The most powerful were nicaeenin F and nicaeenin G. Moreover nicaeenin G significantly stronger sensitized NCI-H460/R cells to DOX than Dex-VER.
PB  - Oxford : Pergamon-Elsevier Science Ltd
T2  - Phytochemistry
T1  - Jatrophane diterpenoids with multidrug-resistance modulating activity from the latex of Euphorbia nicaeensis
VL  - 148
SP  - 104
EP  - 112
DO  - 10.1016/j.phytochem.2018.01.016
ER  - 

@article{
author = "Krstić, Gordana and Jadranin, Milka and Todorović, Nina and Pešić, Milica and Stankovic, Tijana and Aljančić, Ivana and Tešević, Vele",
year = "2018",
abstract = "Seven previously undescribed jatrophane diterpenoids, nicaeenin A-G, with eight known jatrophane diterpenoids, namely euphodendrophanes A-C, F, N, O, Q S, were isolated from latex of Euphorbia nicaeensis collected in Serbia. The chemical structures of the compounds were determined by spectro-scopic analysis including 1D and 2D NMR and HRESIMS experiments. All but one of the previously undescribed jatrophanes, showed significant potential to inhibit P-glycoprotein (P-gp) activity in two MDR cancer cells (NCI-H460/12 and DLD1-TxR). The most powerful were nicaeenin F and nicaeenin G. Moreover nicaeenin G significantly stronger sensitized NCI-H460/R cells to DOX than Dex-VER.",
publisher = "Oxford : Pergamon-Elsevier Science Ltd",
journal = "Phytochemistry",
title = "Jatrophane diterpenoids with multidrug-resistance modulating activity from the latex of Euphorbia nicaeensis",
volume = "148",
pages = "104-112",
doi = "10.1016/j.phytochem.2018.01.016"
}

Krstić, G., Jadranin, M., Todorović, N., Pešić, M., Stankovic, T., Aljančić, I.,& Tešević, V.. (2018). Jatrophane diterpenoids with multidrug-resistance modulating activity from the latex of Euphorbia nicaeensis. in Phytochemistry
Oxford : Pergamon-Elsevier Science Ltd., 148, 104-112.
https://doi.org/10.1016/j.phytochem.2018.01.016

Krstić G, Jadranin M, Todorović N, Pešić M, Stankovic T, Aljančić I, Tešević V. Jatrophane diterpenoids with multidrug-resistance modulating activity from the latex of Euphorbia nicaeensis. in Phytochemistry. 2018;148:104-112.
doi:10.1016/j.phytochem.2018.01.016 .

Krstić, Gordana, Jadranin, Milka, Todorović, Nina, Pešić, Milica, Stankovic, Tijana, Aljančić, Ivana, Tešević, Vele, "Jatrophane diterpenoids with multidrug-resistance modulating activity from the latex of Euphorbia nicaeensis" in Phytochemistry, 148 (2018):104-112,
https://doi.org/10.1016/j.phytochem.2018.01.016 . .

TY  - DATA
AU  - Jeremić, Marko
AU  - Dinić, Jelena
AU  - Pešić, Milica
AU  - Stepanovic, Marija
AU  - Novaković, Irena
AU  - Šegan, Dejan
AU  - Sladić, Dušan
PY  - 2018
UR  - https://www.shd-pub.org.rs/index.php/JSCS/article/view/7014
UR  - https://www.shd-pub.org.rs/index.php/JSCS/article/view/7014/735
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4521
AB  - Additional experimental results, as well as spectroscopic and analytical data
PB  - Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - Supplementary material to: "Alkylamino and aralkylamino derivatives of avarone and its mimetic as selective agents against non-small cell lung cancer cells, their antibacterial and antifungal potential"
UR  - https://hdl.handle.net/21.15107/rcub_cer_4521
ER  - 

@misc{
author = "Jeremić, Marko and Dinić, Jelena and Pešić, Milica and Stepanovic, Marija and Novaković, Irena and Šegan, Dejan and Sladić, Dušan",
year = "2018",
abstract = "Additional experimental results, as well as spectroscopic and analytical data",
publisher = "Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "Supplementary material to: "Alkylamino and aralkylamino derivatives of avarone and its mimetic as selective agents against non-small cell lung cancer cells, their antibacterial and antifungal potential"",
url = "https://hdl.handle.net/21.15107/rcub_cer_4521"
}

Jeremić, M., Dinić, J., Pešić, M., Stepanovic, M., Novaković, I., Šegan, D.,& Sladić, D.. (2018). Supplementary material to: "Alkylamino and aralkylamino derivatives of avarone and its mimetic as selective agents against non-small cell lung cancer cells, their antibacterial and antifungal potential". in Journal of the Serbian Chemical Society
Serbian Chemical Society..
https://hdl.handle.net/21.15107/rcub_cer_4521

Jeremić M, Dinić J, Pešić M, Stepanovic M, Novaković I, Šegan D, Sladić D. Supplementary material to: "Alkylamino and aralkylamino derivatives of avarone and its mimetic as selective agents against non-small cell lung cancer cells, their antibacterial and antifungal potential". in Journal of the Serbian Chemical Society. 2018;.
https://hdl.handle.net/21.15107/rcub_cer_4521 .

Jeremić, Marko, Dinić, Jelena, Pešić, Milica, Stepanovic, Marija, Novaković, Irena, Šegan, Dejan, Sladić, Dušan, "Supplementary material to: "Alkylamino and aralkylamino derivatives of avarone and its mimetic as selective agents against non-small cell lung cancer cells, their antibacterial and antifungal potential"" in Journal of the Serbian Chemical Society (2018),
https://hdl.handle.net/21.15107/rcub_cer_4521 .

TY  - JOUR
AU  - Jeremić, Marko
AU  - Dinić, Jelena
AU  - Pešić, Milica
AU  - Stepanovic, Marija
AU  - Novaković, Irena
AU  - Šegan, Dejan
AU  - Sladić, Dušan
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2361
UR  - https://www.shd-pub.org.rs/index.php/JSCS/article/view/7014
AB  - In this paper, the synthesis of fourteen alkylamino and arylamino derivatives of sesquiterpene quinone avarone and its model compound tert-butylquinone is described. Branched, cyclic, allylic and benzylic alkylamino/arylamino groups were introduced into the quinone moiety. For all the obtained derivatives, their biological activity and redox properties were studied. The cytotoxic activity of the synthesized derivatives towards multidrug resistant (MDR) human non-small cell lung carcinoma NCI-H460/R cells, their sensitive counterpart NCI-H460 and human normal keratinocytes (HaCaT) was investigated. The antimicrobial activity towards Gram-positive and Gram-negative bacteria, and fungal cultures was determined. Some of the synthesized derivatives showed selectivity for cancer cells, including MDR cells. Regarding their cell death induction potential, the most promising compounds were allylamino derivatives, preferentially triggering apoptosis, with high selectivity for cancer cells, including MDR cells. Several compounds showed promising antimicrobial activity, comparable to those of commercial antibiotic and antimycotic agents.
PB  - Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - Alkylamino and aralkylamino derivatives of avarone and its mimetic as selective agents against non-small cell lung cancer cells, their antibacterial and antifungal potential
T1  - Aлкиламино и аралкиламино деривати аварона и његовог миметика као селективни агенси према ћелијама неситноћелијског карцинома плућа, њихов антибактеријски и антифунгални потенцијал
VL  - 83
IS  - 11
SP  - 1193
EP  - 1207
DO  - 10.2298/JSC180627062J
ER  - 

@article{
author = "Jeremić, Marko and Dinić, Jelena and Pešić, Milica and Stepanovic, Marija and Novaković, Irena and Šegan, Dejan and Sladić, Dušan",
year = "2018",
abstract = "In this paper, the synthesis of fourteen alkylamino and arylamino derivatives of sesquiterpene quinone avarone and its model compound tert-butylquinone is described. Branched, cyclic, allylic and benzylic alkylamino/arylamino groups were introduced into the quinone moiety. For all the obtained derivatives, their biological activity and redox properties were studied. The cytotoxic activity of the synthesized derivatives towards multidrug resistant (MDR) human non-small cell lung carcinoma NCI-H460/R cells, their sensitive counterpart NCI-H460 and human normal keratinocytes (HaCaT) was investigated. The antimicrobial activity towards Gram-positive and Gram-negative bacteria, and fungal cultures was determined. Some of the synthesized derivatives showed selectivity for cancer cells, including MDR cells. Regarding their cell death induction potential, the most promising compounds were allylamino derivatives, preferentially triggering apoptosis, with high selectivity for cancer cells, including MDR cells. Several compounds showed promising antimicrobial activity, comparable to those of commercial antibiotic and antimycotic agents.",
publisher = "Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "Alkylamino and aralkylamino derivatives of avarone and its mimetic as selective agents against non-small cell lung cancer cells, their antibacterial and antifungal potential, Aлкиламино и аралкиламино деривати аварона и његовог миметика као селективни агенси према ћелијама неситноћелијског карцинома плућа, њихов антибактеријски и антифунгални потенцијал",
volume = "83",
number = "11",
pages = "1193-1207",
doi = "10.2298/JSC180627062J"
}

Jeremić, M., Dinić, J., Pešić, M., Stepanovic, M., Novaković, I., Šegan, D.,& Sladić, D.. (2018). Alkylamino and aralkylamino derivatives of avarone and its mimetic as selective agents against non-small cell lung cancer cells, their antibacterial and antifungal potential. in Journal of the Serbian Chemical Society
Serbian Chemical Society., 83(11), 1193-1207.
https://doi.org/10.2298/JSC180627062J

Jeremić M, Dinić J, Pešić M, Stepanovic M, Novaković I, Šegan D, Sladić D. Alkylamino and aralkylamino derivatives of avarone and its mimetic as selective agents against non-small cell lung cancer cells, their antibacterial and antifungal potential. in Journal of the Serbian Chemical Society. 2018;83(11):1193-1207.
doi:10.2298/JSC180627062J .

Jeremić, Marko, Dinić, Jelena, Pešić, Milica, Stepanovic, Marija, Novaković, Irena, Šegan, Dejan, Sladić, Dušan, "Alkylamino and aralkylamino derivatives of avarone and its mimetic as selective agents against non-small cell lung cancer cells, their antibacterial and antifungal potential" in Journal of the Serbian Chemical Society, 83, no. 11 (2018):1193-1207,
https://doi.org/10.2298/JSC180627062J . .

TY  - JOUR
AU  - Topalović, Ana
AU  - Knežević, Mirko
AU  - Trifunović, Snežana
AU  - Novaković, Miroslav
AU  - Pešić, Milica
AU  - Ðurović, Dijana
PY  - 2018
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/2886
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2839
AB  - Swiss chard (Beta vulgaris L. var. cicla) is a leafy vegetable highly consumed in many parts of the world as a very popular ingredient of different diets. The purpose of this study was to evaluate effects of soil properties and fertilization on yield, mineral composition, total phenolics, antioxidant and biological activity of Swiss chard. The mineral composition of Swiss chard was generally affected by soil properties. The fertilization at 50% of recommended level (110 kg ha -1 N, 90 kg ha -1 P 2 O 5 and 100 kg ha -1 K 2 O per season) affected negatively yield and on the other hand affected positively antioxidant activity, while fertilization at 150% of recommended level had a contrary effect. The available K in soil affected the yield positively. Total phenolics were in negative correlation with the yield. The positive relationship of total phenolics and content of Mn in chard was noticed. The greatest efficacy in human colorectal carcinoma cell lines was obtained by Swiss chard extract from plants fertilized at 150% of recommended level.
PB  - International Society for Horticultural Science
T2  - European Journal of Horticultural Science
T1  - Effects of soil properties and fertilization on quality and biological activity of Swiss chard
VL  - 83
IS  - 6
SP  - 374
EP  - 381
DO  - 10.17660/eJHS.2018/83.6.5
ER  - 

@article{
author = "Topalović, Ana and Knežević, Mirko and Trifunović, Snežana and Novaković, Miroslav and Pešić, Milica and Ðurović, Dijana",
year = "2018",
abstract = "Swiss chard (Beta vulgaris L. var. cicla) is a leafy vegetable highly consumed in many parts of the world as a very popular ingredient of different diets. The purpose of this study was to evaluate effects of soil properties and fertilization on yield, mineral composition, total phenolics, antioxidant and biological activity of Swiss chard. The mineral composition of Swiss chard was generally affected by soil properties. The fertilization at 50% of recommended level (110 kg ha -1 N, 90 kg ha -1 P 2 O 5 and 100 kg ha -1 K 2 O per season) affected negatively yield and on the other hand affected positively antioxidant activity, while fertilization at 150% of recommended level had a contrary effect. The available K in soil affected the yield positively. Total phenolics were in negative correlation with the yield. The positive relationship of total phenolics and content of Mn in chard was noticed. The greatest efficacy in human colorectal carcinoma cell lines was obtained by Swiss chard extract from plants fertilized at 150% of recommended level.",
publisher = "International Society for Horticultural Science",
journal = "European Journal of Horticultural Science",
title = "Effects of soil properties and fertilization on quality and biological activity of Swiss chard",
volume = "83",
number = "6",
pages = "374-381",
doi = "10.17660/eJHS.2018/83.6.5"
}

Topalović, A., Knežević, M., Trifunović, S., Novaković, M., Pešić, M.,& Ðurović, D.. (2018). Effects of soil properties and fertilization on quality and biological activity of Swiss chard. in European Journal of Horticultural Science
International Society for Horticultural Science., 83(6), 374-381.
https://doi.org/10.17660/eJHS.2018/83.6.5

Topalović A, Knežević M, Trifunović S, Novaković M, Pešić M, Ðurović D. Effects of soil properties and fertilization on quality and biological activity of Swiss chard. in European Journal of Horticultural Science. 2018;83(6):374-381.
doi:10.17660/eJHS.2018/83.6.5 .

Topalović, Ana, Knežević, Mirko, Trifunović, Snežana, Novaković, Miroslav, Pešić, Milica, Ðurović, Dijana, "Effects of soil properties and fertilization on quality and biological activity of Swiss chard" in European Journal of Horticultural Science, 83, no. 6 (2018):374-381,
https://doi.org/10.17660/eJHS.2018/83.6.5 . .

TY  - JOUR
AU  - Jeremić, Marko
AU  - Pešić, Milica
AU  - Dinić, Jelena
AU  - Bankovic, Jasna
AU  - Novaković, Irena
AU  - Šegan, Dejan
AU  - Sladić, Dušan
PY  - 2016
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4579
AB  - In this work, synthesis of alkylamino and aralkylamino derivatives of sesquiterpene quinone avarone and its model compound tert-butylquinone was described. For all obtained derivatives biological activity was studied. Cytotoxic activity of the synthesized derivatives towards multidrug resistant MDR human non small cell lung carcinoma NCI-H460/R cells, their sensitive counterpart NCI-H460 and human normal keratinocytes (HaCaT) as well as detection of cell death superoxide anion generation were investigated. Antimicrobial activity towards Gram positive and Gram negative bacteria and fungal cultures was determined. The results showed that strong cytotoxic activity toward cancer cells was improved with simple avarone mimetics. Some derivatives were selective towards MDR cancer cells. The most active derivatives induced apoptosis in both cancer cell lines, but not in normal cells. Superoxide production was induced by 2,6-disubstituted compounds in MDR cancer cells and not by less active 2,5-disubstituted compounds and was accompanied by the collapse of the mitochondrial transmembrane potential. Two tert-butylquinone derivatives were particularly selective towards MDR cancer cells. Some tert-butylquinone derivatives exhibited a strong antimicrobial activity.
PB  - Elsevier France-Editions Scientifiques Medicales Elsevier, Paris
T2  - European Journal of Medicinal Chemistry
T1  - Simple avarone mimetics as selective agents against multidrug resistant cancer cells
VL  - 118
SP  - 107
EP  - 120
DO  - 10.1016/j.ejmech.2016.04.011
ER  - 

@article{
author = "Jeremić, Marko and Pešić, Milica and Dinić, Jelena and Bankovic, Jasna and Novaković, Irena and Šegan, Dejan and Sladić, Dušan",
year = "2016",
abstract = "In this work, synthesis of alkylamino and aralkylamino derivatives of sesquiterpene quinone avarone and its model compound tert-butylquinone was described. For all obtained derivatives biological activity was studied. Cytotoxic activity of the synthesized derivatives towards multidrug resistant MDR human non small cell lung carcinoma NCI-H460/R cells, their sensitive counterpart NCI-H460 and human normal keratinocytes (HaCaT) as well as detection of cell death superoxide anion generation were investigated. Antimicrobial activity towards Gram positive and Gram negative bacteria and fungal cultures was determined. The results showed that strong cytotoxic activity toward cancer cells was improved with simple avarone mimetics. Some derivatives were selective towards MDR cancer cells. The most active derivatives induced apoptosis in both cancer cell lines, but not in normal cells. Superoxide production was induced by 2,6-disubstituted compounds in MDR cancer cells and not by less active 2,5-disubstituted compounds and was accompanied by the collapse of the mitochondrial transmembrane potential. Two tert-butylquinone derivatives were particularly selective towards MDR cancer cells. Some tert-butylquinone derivatives exhibited a strong antimicrobial activity.",
publisher = "Elsevier France-Editions Scientifiques Medicales Elsevier, Paris",
journal = "European Journal of Medicinal Chemistry",
title = "Simple avarone mimetics as selective agents against multidrug resistant cancer cells",
volume = "118",
pages = "107-120",
doi = "10.1016/j.ejmech.2016.04.011"
}

Jeremić, M., Pešić, M., Dinić, J., Bankovic, J., Novaković, I., Šegan, D.,& Sladić, D.. (2016). Simple avarone mimetics as selective agents against multidrug resistant cancer cells. in European Journal of Medicinal Chemistry
Elsevier France-Editions Scientifiques Medicales Elsevier, Paris., 118, 107-120.
https://doi.org/10.1016/j.ejmech.2016.04.011

Jeremić M, Pešić M, Dinić J, Bankovic J, Novaković I, Šegan D, Sladić D. Simple avarone mimetics as selective agents against multidrug resistant cancer cells. in European Journal of Medicinal Chemistry. 2016;118:107-120.
doi:10.1016/j.ejmech.2016.04.011 .

Jeremić, Marko, Pešić, Milica, Dinić, Jelena, Bankovic, Jasna, Novaković, Irena, Šegan, Dejan, Sladić, Dušan, "Simple avarone mimetics as selective agents against multidrug resistant cancer cells" in European Journal of Medicinal Chemistry, 118 (2016):107-120,
https://doi.org/10.1016/j.ejmech.2016.04.011 . .

TY  - DATA
AU  - Jeremić, Marko
AU  - Pešić, Milica
AU  - Dinić, Jelena
AU  - Bankovic, Jasna
AU  - Novaković, Irena
AU  - Šegan, Dejan
AU  - Sladić, Dušan
PY  - 2016
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4580
AB  - In this work, synthesis of alkylamino and aralkylamino derivatives of sesquiterpene quinone avarone and its model compound tert-butylquinone was described. For all obtained derivatives biological activity was studied. Cytotoxic activity of the synthesized derivatives towards multidrug resistant MDR human non small cell lung carcinoma NCI-H460/R cells, their sensitive counterpart NCI-H460 and human normal keratinocytes (HaCaT) as well as detection of cell death superoxide anion generation were investigated. Antimicrobial activity towards Gram positive and Gram negative bacteria and fungal cultures was determined. The results showed that strong cytotoxic activity toward cancer cells was improved with simple avarone mimetics. Some derivatives were selective towards MDR cancer cells. The most active derivatives induced apoptosis in both cancer cell lines, but not in normal cells. Superoxide production was induced by 2,6-disubstituted compounds in MDR cancer cells and not by less active 2,5-disubstituted compounds and was accompanied by the collapse of the mitochondrial transmembrane potential. Two tert-butylquinone derivatives were particularly selective towards MDR cancer cells. Some tert-butylquinone derivatives exhibited a strong antimicrobial activity.
PB  - Elsevier France-Editions Scientifiques Medicales Elsevier, Paris
T2  - European Journal of Medicinal Chemistry
T1  - Supplementary material for: "Simple avarone mimetics as selective agents against multidrug resistant cancer cells"
UR  - https://hdl.handle.net/21.15107/rcub_cer_4580
ER  - 

@misc{
author = "Jeremić, Marko and Pešić, Milica and Dinić, Jelena and Bankovic, Jasna and Novaković, Irena and Šegan, Dejan and Sladić, Dušan",
year = "2016",
abstract = "In this work, synthesis of alkylamino and aralkylamino derivatives of sesquiterpene quinone avarone and its model compound tert-butylquinone was described. For all obtained derivatives biological activity was studied. Cytotoxic activity of the synthesized derivatives towards multidrug resistant MDR human non small cell lung carcinoma NCI-H460/R cells, their sensitive counterpart NCI-H460 and human normal keratinocytes (HaCaT) as well as detection of cell death superoxide anion generation were investigated. Antimicrobial activity towards Gram positive and Gram negative bacteria and fungal cultures was determined. The results showed that strong cytotoxic activity toward cancer cells was improved with simple avarone mimetics. Some derivatives were selective towards MDR cancer cells. The most active derivatives induced apoptosis in both cancer cell lines, but not in normal cells. Superoxide production was induced by 2,6-disubstituted compounds in MDR cancer cells and not by less active 2,5-disubstituted compounds and was accompanied by the collapse of the mitochondrial transmembrane potential. Two tert-butylquinone derivatives were particularly selective towards MDR cancer cells. Some tert-butylquinone derivatives exhibited a strong antimicrobial activity.",
publisher = "Elsevier France-Editions Scientifiques Medicales Elsevier, Paris",
journal = "European Journal of Medicinal Chemistry",
title = "Supplementary material for: "Simple avarone mimetics as selective agents against multidrug resistant cancer cells"",
url = "https://hdl.handle.net/21.15107/rcub_cer_4580"
}

Jeremić, M., Pešić, M., Dinić, J., Bankovic, J., Novaković, I., Šegan, D.,& Sladić, D.. (2016). Supplementary material for: "Simple avarone mimetics as selective agents against multidrug resistant cancer cells". in European Journal of Medicinal Chemistry
Elsevier France-Editions Scientifiques Medicales Elsevier, Paris..
https://hdl.handle.net/21.15107/rcub_cer_4580

Jeremić M, Pešić M, Dinić J, Bankovic J, Novaković I, Šegan D, Sladić D. Supplementary material for: "Simple avarone mimetics as selective agents against multidrug resistant cancer cells". in European Journal of Medicinal Chemistry. 2016;.
https://hdl.handle.net/21.15107/rcub_cer_4580 .

Jeremić, Marko, Pešić, Milica, Dinić, Jelena, Bankovic, Jasna, Novaković, Irena, Šegan, Dejan, Sladić, Dušan, "Supplementary material for: "Simple avarone mimetics as selective agents against multidrug resistant cancer cells"" in European Journal of Medicinal Chemistry (2016),
https://hdl.handle.net/21.15107/rcub_cer_4580 .

TY  - JOUR
AU  - Dinić, Jelena
AU  - Novaković, Miroslav
AU  - Podolski-Renic, Ana
AU  - Vajs, Vlatka
AU  - Tešević, Vele
AU  - Isaković, Aleksandra
AU  - Pešić, Milica
PY  - 2016
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4162
AB  - Diarylheptanoids represent a group of plant secondary metabolites that possess multiple biological properties and are increasingly recognized for their therapeutic potential. A comparative study was performed on structurally analogous diarylheptanoids isolated from the bark of green (Alnus viridis) and black alder (Alnus glutinosa) to address their biological effects and determine structure-activity relationship. The structures and configurations of all compounds were elucidated by NMR, HR-ESI-MS, UV and IR. Diarylheptanoids actions were studied in human non-small cell lung carcinoma cells (NCI-H460) and normal keratinocytes (HaCaT). A. viridis compounds 3v, 5v, 8v and 9v that possess a carbonyl group at C-3 were considerably more potent than compounds without this group. A. viridis/A. glutinosa analogue pairs, 5v/5g and 9v/9g, which differ in the presence of 30 and 300-OH groups, were evaluated for anticancer activity and selectivity. 5v and 9v that do not possess 30 and 300-OH groups showed significantly higher cytotoxicity compared to analogues 5g and 9g. In addition, these two A. viridis compounds induced a more prominent apoptosis in both cell lines and an increase in subG0 cell cycle phase, compared to their A. glutinosa analogues. 5v and 9v treatment triggered intracellular superoxide anion accumulation and notably decreased mitochondrial transmembrane potential. In HaCaT cells, 9v and 9g with a 4,5 double bond caused a more prominent loss of mitochondrial transmembrane potential compared to 5v and 5g which possess a 5-methoxy group instead. Although green alder diarylheptanoids 5v and 9v displayed higher cytotoxicity, their analogues from black alder 5g and 9g could be more favorable for therapeutic use since they were more active in cancer cells than in normal keratinocytes. These results indicate that minor differences in the chemical structure can greatly influence the effect of diarylheptanoids on apoptosis and redox status and determine their selectivity towards cancer cells.
PB  - Elsevier
T2  - Chemico-Biological Interactions
T1  - Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells
VL  - 249
SP  - 36
EP  - 45
DO  - 10.1016/j.cbi.2016.02.019
ER  - 

@article{
author = "Dinić, Jelena and Novaković, Miroslav and Podolski-Renic, Ana and Vajs, Vlatka and Tešević, Vele and Isaković, Aleksandra and Pešić, Milica",
year = "2016",
abstract = "Diarylheptanoids represent a group of plant secondary metabolites that possess multiple biological properties and are increasingly recognized for their therapeutic potential. A comparative study was performed on structurally analogous diarylheptanoids isolated from the bark of green (Alnus viridis) and black alder (Alnus glutinosa) to address their biological effects and determine structure-activity relationship. The structures and configurations of all compounds were elucidated by NMR, HR-ESI-MS, UV and IR. Diarylheptanoids actions were studied in human non-small cell lung carcinoma cells (NCI-H460) and normal keratinocytes (HaCaT). A. viridis compounds 3v, 5v, 8v and 9v that possess a carbonyl group at C-3 were considerably more potent than compounds without this group. A. viridis/A. glutinosa analogue pairs, 5v/5g and 9v/9g, which differ in the presence of 30 and 300-OH groups, were evaluated for anticancer activity and selectivity. 5v and 9v that do not possess 30 and 300-OH groups showed significantly higher cytotoxicity compared to analogues 5g and 9g. In addition, these two A. viridis compounds induced a more prominent apoptosis in both cell lines and an increase in subG0 cell cycle phase, compared to their A. glutinosa analogues. 5v and 9v treatment triggered intracellular superoxide anion accumulation and notably decreased mitochondrial transmembrane potential. In HaCaT cells, 9v and 9g with a 4,5 double bond caused a more prominent loss of mitochondrial transmembrane potential compared to 5v and 5g which possess a 5-methoxy group instead. Although green alder diarylheptanoids 5v and 9v displayed higher cytotoxicity, their analogues from black alder 5g and 9g could be more favorable for therapeutic use since they were more active in cancer cells than in normal keratinocytes. These results indicate that minor differences in the chemical structure can greatly influence the effect of diarylheptanoids on apoptosis and redox status and determine their selectivity towards cancer cells.",
publisher = "Elsevier",
journal = "Chemico-Biological Interactions",
title = "Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells",
volume = "249",
pages = "36-45",
doi = "10.1016/j.cbi.2016.02.019"
}

Dinić, J., Novaković, M., Podolski-Renic, A., Vajs, V., Tešević, V., Isaković, A.,& Pešić, M.. (2016). Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells. in Chemico-Biological Interactions
Elsevier., 249, 36-45.
https://doi.org/10.1016/j.cbi.2016.02.019

Dinić J, Novaković M, Podolski-Renic A, Vajs V, Tešević V, Isaković A, Pešić M. Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells. in Chemico-Biological Interactions. 2016;249:36-45.
doi:10.1016/j.cbi.2016.02.019 .

Dinić, Jelena, Novaković, Miroslav, Podolski-Renic, Ana, Vajs, Vlatka, Tešević, Vele, Isaković, Aleksandra, Pešić, Milica, "Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells" in Chemico-Biological Interactions, 249 (2016):36-45,
https://doi.org/10.1016/j.cbi.2016.02.019 . .

TY  - JOUR
AU  - Dinić, Jelena
AU  - Novaković, Miroslav
AU  - Podolski-Renic, Ana
AU  - Vajs, Vlatka
AU  - Tešević, Vele
AU  - Isaković, Aleksandra
AU  - Pešić, Milica
PY  - 2016
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1970
AB  - Diarylheptanoids represent a group of plant secondary metabolites that possess multiple biological properties and are increasingly recognized for their therapeutic potential. A comparative study was performed on structurally analogous diarylheptanoids isolated from the bark of green (Alnus viridis) and black alder (Alnus glutinosa) to address their biological effects and determine structure-activity relationship. The structures and configurations of all compounds were elucidated by NMR, HR-ESI-MS, UV and IR. Diarylheptanoids actions were studied in human non-small cell lung carcinoma cells (NCI-H460) and normal keratinocytes (HaCaT). A. viridis compounds 3v, 5v, 8v and 9v that possess a carbonyl group at C-3 were considerably more potent than compounds without this group. A. viridis/A. glutinosa analogue pairs, 5v/5g and 9v/9g, which differ in the presence of 30 and 300-OH groups, were evaluated for anticancer activity and selectivity. 5v and 9v that do not possess 30 and 300-OH groups showed significantly higher cytotoxicity compared to analogues 5g and 9g. In addition, these two A. viridis compounds induced a more prominent apoptosis in both cell lines and an increase in subG0 cell cycle phase, compared to their A. glutinosa analogues. 5v and 9v treatment triggered intracellular superoxide anion accumulation and notably decreased mitochondrial transmembrane potential. In HaCaT cells, 9v and 9g with a 4,5 double bond caused a more prominent loss of mitochondrial transmembrane potential compared to 5v and 5g which possess a 5-methoxy group instead. Although green alder diarylheptanoids 5v and 9v displayed higher cytotoxicity, their analogues from black alder 5g and 9g could be more favorable for therapeutic use since they were more active in cancer cells than in normal keratinocytes. These results indicate that minor differences in the chemical structure can greatly influence the effect of diarylheptanoids on apoptosis and redox status and determine their selectivity towards cancer cells.
PB  - Elsevier Ireland Ltd, Clare
T2  - Chemico-Biological Interactions
T1  - Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells
VL  - 249
SP  - 36
EP  - 45
DO  - 10.1016/j.cbi.2016.02.019
ER  - 

@article{
author = "Dinić, Jelena and Novaković, Miroslav and Podolski-Renic, Ana and Vajs, Vlatka and Tešević, Vele and Isaković, Aleksandra and Pešić, Milica",
year = "2016",
abstract = "Diarylheptanoids represent a group of plant secondary metabolites that possess multiple biological properties and are increasingly recognized for their therapeutic potential. A comparative study was performed on structurally analogous diarylheptanoids isolated from the bark of green (Alnus viridis) and black alder (Alnus glutinosa) to address their biological effects and determine structure-activity relationship. The structures and configurations of all compounds were elucidated by NMR, HR-ESI-MS, UV and IR. Diarylheptanoids actions were studied in human non-small cell lung carcinoma cells (NCI-H460) and normal keratinocytes (HaCaT). A. viridis compounds 3v, 5v, 8v and 9v that possess a carbonyl group at C-3 were considerably more potent than compounds without this group. A. viridis/A. glutinosa analogue pairs, 5v/5g and 9v/9g, which differ in the presence of 30 and 300-OH groups, were evaluated for anticancer activity and selectivity. 5v and 9v that do not possess 30 and 300-OH groups showed significantly higher cytotoxicity compared to analogues 5g and 9g. In addition, these two A. viridis compounds induced a more prominent apoptosis in both cell lines and an increase in subG0 cell cycle phase, compared to their A. glutinosa analogues. 5v and 9v treatment triggered intracellular superoxide anion accumulation and notably decreased mitochondrial transmembrane potential. In HaCaT cells, 9v and 9g with a 4,5 double bond caused a more prominent loss of mitochondrial transmembrane potential compared to 5v and 5g which possess a 5-methoxy group instead. Although green alder diarylheptanoids 5v and 9v displayed higher cytotoxicity, their analogues from black alder 5g and 9g could be more favorable for therapeutic use since they were more active in cancer cells than in normal keratinocytes. These results indicate that minor differences in the chemical structure can greatly influence the effect of diarylheptanoids on apoptosis and redox status and determine their selectivity towards cancer cells.",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Chemico-Biological Interactions",
title = "Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells",
volume = "249",
pages = "36-45",
doi = "10.1016/j.cbi.2016.02.019"
}

Dinić, J., Novaković, M., Podolski-Renic, A., Vajs, V., Tešević, V., Isaković, A.,& Pešić, M.. (2016). Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells. in Chemico-Biological Interactions
Elsevier Ireland Ltd, Clare., 249, 36-45.
https://doi.org/10.1016/j.cbi.2016.02.019

Dinić J, Novaković M, Podolski-Renic A, Vajs V, Tešević V, Isaković A, Pešić M. Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells. in Chemico-Biological Interactions. 2016;249:36-45.
doi:10.1016/j.cbi.2016.02.019 .

Dinić, Jelena, Novaković, Miroslav, Podolski-Renic, Ana, Vajs, Vlatka, Tešević, Vele, Isaković, Aleksandra, Pešić, Milica, "Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells" in Chemico-Biological Interactions, 249 (2016):36-45,
https://doi.org/10.1016/j.cbi.2016.02.019 . .

TY  - JOUR
AU  - Jeremić, Marko
AU  - Pešić, Milica
AU  - Dinić, Jelena
AU  - Bankovic, Jasna
AU  - Novaković, Irena
AU  - Šegan, Dejan
AU  - Sladić, Dušan
PY  - 2016
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1862
AB  - In this work, synthesis of alkylamino and aralkylamino derivatives of sesquiterpene quinone avarone and its model compound tert-butylquinone was described. For all obtained derivatives biological activity was studied. Cytotoxic activity of the synthesized derivatives towards multidrug resistant MDR human non small cell lung carcinoma NCI-H460/R cells, their sensitive counterpart NCI-H460 and human normal keratinocytes (HaCaT) as well as detection of cell death superoxide anion generation were investigated. Antimicrobial activity towards Gram positive and Gram negative bacteria and fungal cultures was determined. The results showed that strong cytotoxic activity toward cancer cells was improved with simple avarone mimetics. Some derivatives were selective towards MDR cancer cells. The most active derivatives induced apoptosis in both cancer cell lines, but not in normal cells. Superoxide production was induced by 2,6-disubstituted compounds in MDR cancer cells and not by less active 2,5-disubstituted compounds and was accompanied by the collapse of the mitochondrial transmembrane potential. Two tert-butylquinone derivatives were particularly selective towards MDR cancer cells. Some tert-butylquinone derivatives exhibited a strong antimicrobial activity.
PB  - Elsevier France-Editions Scientifiques Medicales Elsevier, Paris
T2  - European Journal of Medicinal Chemistry
T1  - Simple avarone mimetics as selective agents against multidrug resistant cancer cells
VL  - 118
SP  - 107
EP  - 120
DO  - 10.1016/j.ejmech.2016.04.011
ER  - 

@article{
author = "Jeremić, Marko and Pešić, Milica and Dinić, Jelena and Bankovic, Jasna and Novaković, Irena and Šegan, Dejan and Sladić, Dušan",
year = "2016",
abstract = "In this work, synthesis of alkylamino and aralkylamino derivatives of sesquiterpene quinone avarone and its model compound tert-butylquinone was described. For all obtained derivatives biological activity was studied. Cytotoxic activity of the synthesized derivatives towards multidrug resistant MDR human non small cell lung carcinoma NCI-H460/R cells, their sensitive counterpart NCI-H460 and human normal keratinocytes (HaCaT) as well as detection of cell death superoxide anion generation were investigated. Antimicrobial activity towards Gram positive and Gram negative bacteria and fungal cultures was determined. The results showed that strong cytotoxic activity toward cancer cells was improved with simple avarone mimetics. Some derivatives were selective towards MDR cancer cells. The most active derivatives induced apoptosis in both cancer cell lines, but not in normal cells. Superoxide production was induced by 2,6-disubstituted compounds in MDR cancer cells and not by less active 2,5-disubstituted compounds and was accompanied by the collapse of the mitochondrial transmembrane potential. Two tert-butylquinone derivatives were particularly selective towards MDR cancer cells. Some tert-butylquinone derivatives exhibited a strong antimicrobial activity.",
publisher = "Elsevier France-Editions Scientifiques Medicales Elsevier, Paris",
journal = "European Journal of Medicinal Chemistry",
title = "Simple avarone mimetics as selective agents against multidrug resistant cancer cells",
volume = "118",
pages = "107-120",
doi = "10.1016/j.ejmech.2016.04.011"
}

Jeremić, M., Pešić, M., Dinić, J., Bankovic, J., Novaković, I., Šegan, D.,& Sladić, D.. (2016). Simple avarone mimetics as selective agents against multidrug resistant cancer cells. in European Journal of Medicinal Chemistry
Elsevier France-Editions Scientifiques Medicales Elsevier, Paris., 118, 107-120.
https://doi.org/10.1016/j.ejmech.2016.04.011

Jeremić M, Pešić M, Dinić J, Bankovic J, Novaković I, Šegan D, Sladić D. Simple avarone mimetics as selective agents against multidrug resistant cancer cells. in European Journal of Medicinal Chemistry. 2016;118:107-120.
doi:10.1016/j.ejmech.2016.04.011 .

Jeremić, Marko, Pešić, Milica, Dinić, Jelena, Bankovic, Jasna, Novaković, Irena, Šegan, Dejan, Sladić, Dušan, "Simple avarone mimetics as selective agents against multidrug resistant cancer cells" in European Journal of Medicinal Chemistry, 118 (2016):107-120,
https://doi.org/10.1016/j.ejmech.2016.04.011 . .

TY  - JOUR
AU  - Dinić, Jelena
AU  - Randelovic, Teodora
AU  - Stankovic, Tijana
AU  - Dragoj, Miodrag
AU  - Isaković, Aleksandra
AU  - Novaković, Miroslav
AU  - Pešić, Milica
PY  - 2015
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3185
AB  - Medicinal plants are recognized from ancient times as a source of diverse therapeutic agents and many of them are used as dietary supplements. Comprehensive approaches are needed that would identify bioactive components with evident activity against specific indications and provide a better link between science (ethno-botany, chemistry, biology and pharmacology) and market Recently, the bark of black alder (Alnus glutinosa) appeared at market in the form of food supplement for treatment of different skin conditions. This study aimed to evaluate protective effects of two diarylheptanoids isolated from the bark of black alder: platyphylloside, 5(S)-1,7-di(4-hydroxyphenyl)-3-heptanone-5-O-beta-D-glucopyranoside (1) and its newly discovered analog 5(S)-1,7-di(4-hydroxyphenyl)-5-O-beta-D-[6-(E-p-coumaroylglucopyranosyl)]heptane-3-one (2) towards doxorubicin damaging activity. To that end, we employed HaCaT cells, non-cancerous human keratinocytes commonly used for skin regenerative studies. Diarylheptanoids significantly antagonized the effects of doxorubicin by lowering the sensitivity of HaCaT cells to this drug. Compound 2 prevented doxorubicin-induced cell death by activating autophagy. Both land 2 protected HaCaT cells against doxorubicin-induced DNA damage. They significantly promoted migration and affected F-actin distribution. These results indicate that chemo-protective effects of diarylheptanoids may occur at multiple subcellular levels. Therefore, diarylheptanoids 1 and 2 could be considered as protective agents for non-cancerous dividing cells during chemotherapy.
PB  - Elsevier
T2  - Fitoterapia
T1  - Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes
VL  - 105
SP  - 169
EP  - 176
DO  - 10.1016/j.fitote.2015.07.003
ER  - 

@article{
author = "Dinić, Jelena and Randelovic, Teodora and Stankovic, Tijana and Dragoj, Miodrag and Isaković, Aleksandra and Novaković, Miroslav and Pešić, Milica",
year = "2015",
abstract = "Medicinal plants are recognized from ancient times as a source of diverse therapeutic agents and many of them are used as dietary supplements. Comprehensive approaches are needed that would identify bioactive components with evident activity against specific indications and provide a better link between science (ethno-botany, chemistry, biology and pharmacology) and market Recently, the bark of black alder (Alnus glutinosa) appeared at market in the form of food supplement for treatment of different skin conditions. This study aimed to evaluate protective effects of two diarylheptanoids isolated from the bark of black alder: platyphylloside, 5(S)-1,7-di(4-hydroxyphenyl)-3-heptanone-5-O-beta-D-glucopyranoside (1) and its newly discovered analog 5(S)-1,7-di(4-hydroxyphenyl)-5-O-beta-D-[6-(E-p-coumaroylglucopyranosyl)]heptane-3-one (2) towards doxorubicin damaging activity. To that end, we employed HaCaT cells, non-cancerous human keratinocytes commonly used for skin regenerative studies. Diarylheptanoids significantly antagonized the effects of doxorubicin by lowering the sensitivity of HaCaT cells to this drug. Compound 2 prevented doxorubicin-induced cell death by activating autophagy. Both land 2 protected HaCaT cells against doxorubicin-induced DNA damage. They significantly promoted migration and affected F-actin distribution. These results indicate that chemo-protective effects of diarylheptanoids may occur at multiple subcellular levels. Therefore, diarylheptanoids 1 and 2 could be considered as protective agents for non-cancerous dividing cells during chemotherapy.",
publisher = "Elsevier",
journal = "Fitoterapia",
title = "Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes",
volume = "105",
pages = "169-176",
doi = "10.1016/j.fitote.2015.07.003"
}

Dinić, J., Randelovic, T., Stankovic, T., Dragoj, M., Isaković, A., Novaković, M.,& Pešić, M.. (2015). Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes. in Fitoterapia
Elsevier., 105, 169-176.
https://doi.org/10.1016/j.fitote.2015.07.003

Dinić J, Randelovic T, Stankovic T, Dragoj M, Isaković A, Novaković M, Pešić M. Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes. in Fitoterapia. 2015;105:169-176.
doi:10.1016/j.fitote.2015.07.003 .

Dinić, Jelena, Randelovic, Teodora, Stankovic, Tijana, Dragoj, Miodrag, Isaković, Aleksandra, Novaković, Miroslav, Pešić, Milica, "Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes" in Fitoterapia, 105 (2015):169-176,
https://doi.org/10.1016/j.fitote.2015.07.003 . .

TY  - JOUR
AU  - Dinić, Jelena
AU  - Randelovic, Teodora
AU  - Stankovic, Tijana
AU  - Dragoj, Miodrag
AU  - Isaković, Aleksandra
AU  - Novaković, Miroslav
AU  - Pešić, Milica
PY  - 2015
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1668
AB  - Medicinal plants are recognized from ancient times as a source of diverse therapeutic agents and many of them are used as dietary supplements. Comprehensive approaches are needed that would identify bioactive components with evident activity against specific indications and provide a better link between science (ethno-botany, chemistry, biology and pharmacology) and market Recently, the bark of black alder (Alnus glutinosa) appeared at market in the form of food supplement for treatment of different skin conditions. This study aimed to evaluate protective effects of two diarylheptanoids isolated from the bark of black alder: platyphylloside, 5(S)-1,7-di(4-hydroxyphenyl)-3-heptanone-5-O-beta-D-glucopyranoside (1) and its newly discovered analog 5(S)-1,7-di(4-hydroxyphenyl)-5-O-beta-D-[6-(E-p-coumaroylglucopyranosyl)]heptane-3-one (2) towards doxorubicin damaging activity. To that end, we employed HaCaT cells, non-cancerous human keratinocytes commonly used for skin regenerative studies. Diarylheptanoids significantly antagonized the effects of doxorubicin by lowering the sensitivity of HaCaT cells to this drug. Compound 2 prevented doxorubicin-induced cell death by activating autophagy. Both land 2 protected HaCaT cells against doxorubicin-induced DNA damage. They significantly promoted migration and affected F-actin distribution. These results indicate that chemo-protective effects of diarylheptanoids may occur at multiple subcellular levels. Therefore, diarylheptanoids 1 and 2 could be considered as protective agents for non-cancerous dividing cells during chemotherapy.
PB  - Elsevier
T2  - Fitoterapia
T1  - Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes
VL  - 105
SP  - 169
EP  - 176
DO  - 10.1016/j.fitote.2015.07.003
ER  - 

@article{
author = "Dinić, Jelena and Randelovic, Teodora and Stankovic, Tijana and Dragoj, Miodrag and Isaković, Aleksandra and Novaković, Miroslav and Pešić, Milica",
year = "2015",
abstract = "Medicinal plants are recognized from ancient times as a source of diverse therapeutic agents and many of them are used as dietary supplements. Comprehensive approaches are needed that would identify bioactive components with evident activity against specific indications and provide a better link between science (ethno-botany, chemistry, biology and pharmacology) and market Recently, the bark of black alder (Alnus glutinosa) appeared at market in the form of food supplement for treatment of different skin conditions. This study aimed to evaluate protective effects of two diarylheptanoids isolated from the bark of black alder: platyphylloside, 5(S)-1,7-di(4-hydroxyphenyl)-3-heptanone-5-O-beta-D-glucopyranoside (1) and its newly discovered analog 5(S)-1,7-di(4-hydroxyphenyl)-5-O-beta-D-[6-(E-p-coumaroylglucopyranosyl)]heptane-3-one (2) towards doxorubicin damaging activity. To that end, we employed HaCaT cells, non-cancerous human keratinocytes commonly used for skin regenerative studies. Diarylheptanoids significantly antagonized the effects of doxorubicin by lowering the sensitivity of HaCaT cells to this drug. Compound 2 prevented doxorubicin-induced cell death by activating autophagy. Both land 2 protected HaCaT cells against doxorubicin-induced DNA damage. They significantly promoted migration and affected F-actin distribution. These results indicate that chemo-protective effects of diarylheptanoids may occur at multiple subcellular levels. Therefore, diarylheptanoids 1 and 2 could be considered as protective agents for non-cancerous dividing cells during chemotherapy.",
publisher = "Elsevier",
journal = "Fitoterapia",
title = "Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes",
volume = "105",
pages = "169-176",
doi = "10.1016/j.fitote.2015.07.003"
}

Dinić, J., Randelovic, T., Stankovic, T., Dragoj, M., Isaković, A., Novaković, M.,& Pešić, M.. (2015). Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes. in Fitoterapia
Elsevier., 105, 169-176.
https://doi.org/10.1016/j.fitote.2015.07.003

Dinić J, Randelovic T, Stankovic T, Dragoj M, Isaković A, Novaković M, Pešić M. Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes. in Fitoterapia. 2015;105:169-176.
doi:10.1016/j.fitote.2015.07.003 .

Dinić, Jelena, Randelovic, Teodora, Stankovic, Tijana, Dragoj, Miodrag, Isaković, Aleksandra, Novaković, Miroslav, Pešić, Milica, "Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes" in Fitoterapia, 105 (2015):169-176,
https://doi.org/10.1016/j.fitote.2015.07.003 . .

TY  - JOUR
AU  - Novaković, Miroslav
AU  - Pešić, Milica
AU  - Trifunović, Snežana
AU  - Vučković, Ivan
AU  - Todorović, Nina
AU  - Podolski-Renic, Ana
AU  - Dinić, Jelena
AU  - Stojkovic, Sonja
AU  - Tešević, Vele
AU  - Vajs, Vlatka
AU  - Milosavljević, Slobodan
PY  - 2014
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1549
AB  - An extended study of minor diarylheptanoids from the bark of black alder has resulted in the isolation of twenty diarylheptanoids, ten of which have not previously been reported (14-18, 20-24). The structures and configurations of all compounds were elucidated by NMR, HRESIMS, UV, IR, and CD. The anti-cancer potency of twenty diarylheptanoids and four previously isolated compounds (7, 10, 12, 13) was investigated in human non-small cell lung carcinoma cell lines (sensitive and multi-drug resistant variants) as well as in normal human keratinocytes. Diarylheptanoids with a p-coumaroyl group, 14 and 18, platyphylloside (1), platyphyllonol-5-O-beta-D-xylopyranoside (2), alnuside B (4) and hirsutenone (9) exhibited strong anti-cancer activity, considerably higher than diarylheptanoid curcumin, which served as a positive control. Compounds 4, 9, 14, and 18 displayed significant selectivity towards the cancer cells. Structure/activity analysis of twenty-four closely related diarylheptanoids revealed a high dependence of cytotoxic action on the presence of a carbonyl group at C-3. Substitution of a heptane chain on C-5 and a number of hydroxyl groups in the aromatic rings also emerged as a significant structural feature that influenced their cytotoxic potential.
PB  - Oxford : Pergamon-Elsevier Science Ltd
T2  - Phytochemistry
T1  - Diarylheptanoids from the bark of black alder inhibit the growth of sensitive and multi-drug resistant non-small cell lung carcinoma cells
VL  - 97
SP  - 46
EP  - 54
DO  - 10.1016/j.phytochem.2013.11.001
ER  - 

@article{
author = "Novaković, Miroslav and Pešić, Milica and Trifunović, Snežana and Vučković, Ivan and Todorović, Nina and Podolski-Renic, Ana and Dinić, Jelena and Stojkovic, Sonja and Tešević, Vele and Vajs, Vlatka and Milosavljević, Slobodan",
year = "2014",
abstract = "An extended study of minor diarylheptanoids from the bark of black alder has resulted in the isolation of twenty diarylheptanoids, ten of which have not previously been reported (14-18, 20-24). The structures and configurations of all compounds were elucidated by NMR, HRESIMS, UV, IR, and CD. The anti-cancer potency of twenty diarylheptanoids and four previously isolated compounds (7, 10, 12, 13) was investigated in human non-small cell lung carcinoma cell lines (sensitive and multi-drug resistant variants) as well as in normal human keratinocytes. Diarylheptanoids with a p-coumaroyl group, 14 and 18, platyphylloside (1), platyphyllonol-5-O-beta-D-xylopyranoside (2), alnuside B (4) and hirsutenone (9) exhibited strong anti-cancer activity, considerably higher than diarylheptanoid curcumin, which served as a positive control. Compounds 4, 9, 14, and 18 displayed significant selectivity towards the cancer cells. Structure/activity analysis of twenty-four closely related diarylheptanoids revealed a high dependence of cytotoxic action on the presence of a carbonyl group at C-3. Substitution of a heptane chain on C-5 and a number of hydroxyl groups in the aromatic rings also emerged as a significant structural feature that influenced their cytotoxic potential.",
publisher = "Oxford : Pergamon-Elsevier Science Ltd",
journal = "Phytochemistry",
title = "Diarylheptanoids from the bark of black alder inhibit the growth of sensitive and multi-drug resistant non-small cell lung carcinoma cells",
volume = "97",
pages = "46-54",
doi = "10.1016/j.phytochem.2013.11.001"
}

Novaković, M., Pešić, M., Trifunović, S., Vučković, I., Todorović, N., Podolski-Renic, A., Dinić, J., Stojkovic, S., Tešević, V., Vajs, V.,& Milosavljević, S.. (2014). Diarylheptanoids from the bark of black alder inhibit the growth of sensitive and multi-drug resistant non-small cell lung carcinoma cells. in Phytochemistry
Oxford : Pergamon-Elsevier Science Ltd., 97, 46-54.
https://doi.org/10.1016/j.phytochem.2013.11.001

Novaković M, Pešić M, Trifunović S, Vučković I, Todorović N, Podolski-Renic A, Dinić J, Stojkovic S, Tešević V, Vajs V, Milosavljević S. Diarylheptanoids from the bark of black alder inhibit the growth of sensitive and multi-drug resistant non-small cell lung carcinoma cells. in Phytochemistry. 2014;97:46-54.
doi:10.1016/j.phytochem.2013.11.001 .

Novaković, Miroslav, Pešić, Milica, Trifunović, Snežana, Vučković, Ivan, Todorović, Nina, Podolski-Renic, Ana, Dinić, Jelena, Stojkovic, Sonja, Tešević, Vele, Vajs, Vlatka, Milosavljević, Slobodan, "Diarylheptanoids from the bark of black alder inhibit the growth of sensitive and multi-drug resistant non-small cell lung carcinoma cells" in Phytochemistry, 97 (2014):46-54,
https://doi.org/10.1016/j.phytochem.2013.11.001 . .

TY  - JOUR
AU  - Dinić, Jelena
AU  - Novaković, Miroslav
AU  - Podolski-Renic, Ana
AU  - Stojkovic, Sonja
AU  - Mandić, Boris
AU  - Tešević, Vele
AU  - Vajs, Vlatka
AU  - Isaković, Aleksandra
AU  - Pešić, Milica
PY  - 2014
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1434
AB  - Diarylheptanoids belong to polyphenols, a group of plant secondary metabolites with multiple biological properties. Many of them display antioxidative, cytotoxic, or anticancer actions and are increasingly recognized as potential therapeutic agents. The aim of this study was to evaluate antioxidant and cytoprotective activity of two diarylheptanoids: platyphylloside 5(S)-1,7-di(4-hydroxyphenyl)-3-heptanone-5-O-beta-D-glucopyranoside (1) and its newly discovered analog 5(S)-1,7-di(4-hydroxyphenyl)-5-O-beta-D-[6-(E-p-coumaroylglucopyranosyl)]heptane-3-one (2), both isolated from the bark of black alder (Alnus glutinosa). To that end, we have employed a cancer cell line (NCI-H460), normal human keratinocytes (HaCaT), and peripheral blood mononuclear cells. The effects on cell growth were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Cell death was examined by annexin V/propidium iodide staining on a flow cytometer. Reactive oxygen species production was examined by dihydroethidium staining. Mitochondrial structure and doxorubicin localization were visualized by fluorescent microscopy. Gene expression of manganese superoxide dismutase and hypoxia-inducible factor-1 alpha was determined by reverse transcription polymerase chain reaction. Diarylheptanoids antagonized the effects of either doxorubicin or cisplatin, significantly increasing their IC50 values in normal cells. Diarylheptanoid 1 induced the retention of doxorubicin in cytoplasm and reduced mitochondrial fragmentation associated with doxorubicin application. Diarylheptanoid 2 reduced the reactive oxygen species production induced by cisplatin. Both compounds increased the messenger ribonucleic acid expression of enzymes involved in reactive oxygen species elimination (manganese superoxide dismutase and hypoxia-inducible factor-1 alpha). These results indicate that neutralization of reactive oxygen species is an important mechanism of diarylheptanoid action, although these compounds exert a considerable anticancer effect. Therefore, these compounds may serve as protectors of normal cells during chemotherapy without significantly diminishing the effect of the applied chemotherapeutic.
PB  - Georg Thieme Verlag Kg, Stuttgart
T2  - Planta Medica
T1  - Antioxidative Activity of Diarylheptanoids from the Bark of Black Alder (Alnus glutinosa) and Their Interaction with Anticancer Drugs
VL  - 80
IS  - 13
SP  - 1088
EP  - 1096
DO  - 10.1055/s-0034-1382993
ER  - 

@article{
author = "Dinić, Jelena and Novaković, Miroslav and Podolski-Renic, Ana and Stojkovic, Sonja and Mandić, Boris and Tešević, Vele and Vajs, Vlatka and Isaković, Aleksandra and Pešić, Milica",
year = "2014",
abstract = "Diarylheptanoids belong to polyphenols, a group of plant secondary metabolites with multiple biological properties. Many of them display antioxidative, cytotoxic, or anticancer actions and are increasingly recognized as potential therapeutic agents. The aim of this study was to evaluate antioxidant and cytoprotective activity of two diarylheptanoids: platyphylloside 5(S)-1,7-di(4-hydroxyphenyl)-3-heptanone-5-O-beta-D-glucopyranoside (1) and its newly discovered analog 5(S)-1,7-di(4-hydroxyphenyl)-5-O-beta-D-[6-(E-p-coumaroylglucopyranosyl)]heptane-3-one (2), both isolated from the bark of black alder (Alnus glutinosa). To that end, we have employed a cancer cell line (NCI-H460), normal human keratinocytes (HaCaT), and peripheral blood mononuclear cells. The effects on cell growth were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Cell death was examined by annexin V/propidium iodide staining on a flow cytometer. Reactive oxygen species production was examined by dihydroethidium staining. Mitochondrial structure and doxorubicin localization were visualized by fluorescent microscopy. Gene expression of manganese superoxide dismutase and hypoxia-inducible factor-1 alpha was determined by reverse transcription polymerase chain reaction. Diarylheptanoids antagonized the effects of either doxorubicin or cisplatin, significantly increasing their IC50 values in normal cells. Diarylheptanoid 1 induced the retention of doxorubicin in cytoplasm and reduced mitochondrial fragmentation associated with doxorubicin application. Diarylheptanoid 2 reduced the reactive oxygen species production induced by cisplatin. Both compounds increased the messenger ribonucleic acid expression of enzymes involved in reactive oxygen species elimination (manganese superoxide dismutase and hypoxia-inducible factor-1 alpha). These results indicate that neutralization of reactive oxygen species is an important mechanism of diarylheptanoid action, although these compounds exert a considerable anticancer effect. Therefore, these compounds may serve as protectors of normal cells during chemotherapy without significantly diminishing the effect of the applied chemotherapeutic.",
publisher = "Georg Thieme Verlag Kg, Stuttgart",
journal = "Planta Medica",
title = "Antioxidative Activity of Diarylheptanoids from the Bark of Black Alder (Alnus glutinosa) and Their Interaction with Anticancer Drugs",
volume = "80",
number = "13",
pages = "1088-1096",
doi = "10.1055/s-0034-1382993"
}

Dinić, J., Novaković, M., Podolski-Renic, A., Stojkovic, S., Mandić, B., Tešević, V., Vajs, V., Isaković, A.,& Pešić, M.. (2014). Antioxidative Activity of Diarylheptanoids from the Bark of Black Alder (Alnus glutinosa) and Their Interaction with Anticancer Drugs. in Planta Medica
Georg Thieme Verlag Kg, Stuttgart., 80(13), 1088-1096.
https://doi.org/10.1055/s-0034-1382993

Dinić J, Novaković M, Podolski-Renic A, Stojkovic S, Mandić B, Tešević V, Vajs V, Isaković A, Pešić M. Antioxidative Activity of Diarylheptanoids from the Bark of Black Alder (Alnus glutinosa) and Their Interaction with Anticancer Drugs. in Planta Medica. 2014;80(13):1088-1096.
doi:10.1055/s-0034-1382993 .

Dinić, Jelena, Novaković, Miroslav, Podolski-Renic, Ana, Stojkovic, Sonja, Mandić, Boris, Tešević, Vele, Vajs, Vlatka, Isaković, Aleksandra, Pešić, Milica, "Antioxidative Activity of Diarylheptanoids from the Bark of Black Alder (Alnus glutinosa) and Their Interaction with Anticancer Drugs" in Planta Medica, 80, no. 13 (2014):1088-1096,
https://doi.org/10.1055/s-0034-1382993 . .

TY  - JOUR
AU  - Aljančić, Ivana
AU  - Vučković, Ivan
AU  - Jadranin, Milka
AU  - Pešić, Milica
AU  - Đorđević, Iris
AU  - Podolski-Renic, Ana
AU  - Stojkovic, Sonja
AU  - Menković, Nebojša
AU  - Vajs, Vlatka
AU  - Milosavljević, Slobodan
PY  - 2014
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1542
AB  - Dimers tomoroside A (1) and tomoroside B (2) of the co-occuring known chalcone monomer (3), along with the seven known flavonoid glucosides (4-10), were isolated from the aerial parts of Helichrysum zivojinii Cernjavski & Soska. The structures of the isolated compounds were elucidated by spectroscopic techniques. Compound 1 inhibited topo Ha and hif-1 alpha expression and stimulated doxorubicin anticancer effect, while 2 increased the expression of hif-1 alpha a, probably acting as antioxidant and redox status modulator. Notably, 2 synergized with Tipifarnib showing potential to improve the action of this new chemotherapeutic involved in the modulation of mitogene activated protein (MAP) kinase signaling pathway.
PB  - Oxford : Pergamon-Elsevier Science Ltd
T2  - Phytochemistry
T1  - Two structurally distinct chalcone dimers from Helichrysum zivojinii and their activities in cancer cell lines
VL  - 98
SP  - 190
EP  - 196
DO  - 10.1016/j.phytochem.2013.11.025
ER  - 

@article{
author = "Aljančić, Ivana and Vučković, Ivan and Jadranin, Milka and Pešić, Milica and Đorđević, Iris and Podolski-Renic, Ana and Stojkovic, Sonja and Menković, Nebojša and Vajs, Vlatka and Milosavljević, Slobodan",
year = "2014",
abstract = "Dimers tomoroside A (1) and tomoroside B (2) of the co-occuring known chalcone monomer (3), along with the seven known flavonoid glucosides (4-10), were isolated from the aerial parts of Helichrysum zivojinii Cernjavski & Soska. The structures of the isolated compounds were elucidated by spectroscopic techniques. Compound 1 inhibited topo Ha and hif-1 alpha expression and stimulated doxorubicin anticancer effect, while 2 increased the expression of hif-1 alpha a, probably acting as antioxidant and redox status modulator. Notably, 2 synergized with Tipifarnib showing potential to improve the action of this new chemotherapeutic involved in the modulation of mitogene activated protein (MAP) kinase signaling pathway.",
publisher = "Oxford : Pergamon-Elsevier Science Ltd",
journal = "Phytochemistry",
title = "Two structurally distinct chalcone dimers from Helichrysum zivojinii and their activities in cancer cell lines",
volume = "98",
pages = "190-196",
doi = "10.1016/j.phytochem.2013.11.025"
}

Aljančić, I., Vučković, I., Jadranin, M., Pešić, M., Đorđević, I., Podolski-Renic, A., Stojkovic, S., Menković, N., Vajs, V.,& Milosavljević, S.. (2014). Two structurally distinct chalcone dimers from Helichrysum zivojinii and their activities in cancer cell lines. in Phytochemistry
Oxford : Pergamon-Elsevier Science Ltd., 98, 190-196.
https://doi.org/10.1016/j.phytochem.2013.11.025

Aljančić I, Vučković I, Jadranin M, Pešić M, Đorđević I, Podolski-Renic A, Stojkovic S, Menković N, Vajs V, Milosavljević S. Two structurally distinct chalcone dimers from Helichrysum zivojinii and their activities in cancer cell lines. in Phytochemistry. 2014;98:190-196.
doi:10.1016/j.phytochem.2013.11.025 .

Aljančić, Ivana, Vučković, Ivan, Jadranin, Milka, Pešić, Milica, Đorđević, Iris, Podolski-Renic, Ana, Stojkovic, Sonja, Menković, Nebojša, Vajs, Vlatka, Milosavljević, Slobodan, "Two structurally distinct chalcone dimers from Helichrysum zivojinii and their activities in cancer cell lines" in Phytochemistry, 98 (2014):190-196,
https://doi.org/10.1016/j.phytochem.2013.11.025 . .

TY  - JOUR
AU  - Jadranin, Milka
AU  - Pešić, Milica
AU  - Aljančić, Ivana
AU  - Milosavljević, Slobodan
AU  - Todorović, Nina
AU  - Podolski-Renic, Ana
AU  - Bankovic, Jasna
AU  - Tanic, Nikola
AU  - Markovic, Ivanka
AU  - Vajs, Vlatka
AU  - Tešević, Vele
PY  - 2013
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1278
AB  - Thirteen jatrophane diterpenoids (1-10, 13-15), three previously isolated (11, 12, 16) and a known tigliane (17) were isolated from the latex of Euphorbia dendroides. The structures and relative configurations of compounds were elucidated by spectroscopic techniques. The P-glycoprotein (P-gp) inhibiting activities of the representative set of jatrophanes (1-6 and 11-16) have been assessed. Jatrophanes 2 and 5 demonstrated the most powerful inhibition of P-gp, higher than R(+)-verapamil and tariquidar in colorectal multi-drug resistant (MDR) cells (DLD1-TxR).
PB  - Oxford : Pergamon-Elsevier Science Ltd
T2  - Phytochemistry
T1  - Jatrophane diterpenoids from the latex of Euphorbia dendroides and their anti-P-glycoprotein activity in human multi-drug resistant cancer cell lines
VL  - 86
SP  - 208
EP  - 217
DO  - 10.1016/j.phytochem.2012.09.003
ER  - 

@article{
author = "Jadranin, Milka and Pešić, Milica and Aljančić, Ivana and Milosavljević, Slobodan and Todorović, Nina and Podolski-Renic, Ana and Bankovic, Jasna and Tanic, Nikola and Markovic, Ivanka and Vajs, Vlatka and Tešević, Vele",
year = "2013",
abstract = "Thirteen jatrophane diterpenoids (1-10, 13-15), three previously isolated (11, 12, 16) and a known tigliane (17) were isolated from the latex of Euphorbia dendroides. The structures and relative configurations of compounds were elucidated by spectroscopic techniques. The P-glycoprotein (P-gp) inhibiting activities of the representative set of jatrophanes (1-6 and 11-16) have been assessed. Jatrophanes 2 and 5 demonstrated the most powerful inhibition of P-gp, higher than R(+)-verapamil and tariquidar in colorectal multi-drug resistant (MDR) cells (DLD1-TxR).",
publisher = "Oxford : Pergamon-Elsevier Science Ltd",
journal = "Phytochemistry",
title = "Jatrophane diterpenoids from the latex of Euphorbia dendroides and their anti-P-glycoprotein activity in human multi-drug resistant cancer cell lines",
volume = "86",
pages = "208-217",
doi = "10.1016/j.phytochem.2012.09.003"
}

Jadranin, M., Pešić, M., Aljančić, I., Milosavljević, S., Todorović, N., Podolski-Renic, A., Bankovic, J., Tanic, N., Markovic, I., Vajs, V.,& Tešević, V.. (2013). Jatrophane diterpenoids from the latex of Euphorbia dendroides and their anti-P-glycoprotein activity in human multi-drug resistant cancer cell lines. in Phytochemistry
Oxford : Pergamon-Elsevier Science Ltd., 86, 208-217.
https://doi.org/10.1016/j.phytochem.2012.09.003

Jadranin M, Pešić M, Aljančić I, Milosavljević S, Todorović N, Podolski-Renic A, Bankovic J, Tanic N, Markovic I, Vajs V, Tešević V. Jatrophane diterpenoids from the latex of Euphorbia dendroides and their anti-P-glycoprotein activity in human multi-drug resistant cancer cell lines. in Phytochemistry. 2013;86:208-217.
doi:10.1016/j.phytochem.2012.09.003 .

Jadranin, Milka, Pešić, Milica, Aljančić, Ivana, Milosavljević, Slobodan, Todorović, Nina, Podolski-Renic, Ana, Bankovic, Jasna, Tanic, Nikola, Markovic, Ivanka, Vajs, Vlatka, Tešević, Vele, "Jatrophane diterpenoids from the latex of Euphorbia dendroides and their anti-P-glycoprotein activity in human multi-drug resistant cancer cell lines" in Phytochemistry, 86 (2013):208-217,
https://doi.org/10.1016/j.phytochem.2012.09.003 . .

TY  - JOUR
AU  - Podolski-Renic, Ana
AU  - Jadranin, Milka
AU  - Stankovic, Tijana
AU  - Bankovic, Jasna
AU  - Stojkovic, Sonja
AU  - Chiourea, Maria
AU  - Aljančić, Ivana
AU  - Vajs, Vlatka
AU  - Tešević, Vele
AU  - Ruzdijic, Sabera
AU  - Gagos, Sarantis
AU  - Tanic, Nikola
AU  - Pešić, Milica
PY  - 2013
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1176
AB  - Multi-drug resistance (MDR) is a major obstacle to successful cancer treatment. Therefore, in vitro models are necessary for the investigation of the phenotypic changes provoked by cytotoxic agents and more importantly for preclinical testing of new anticancer drugs. We analyzed chromosomal, numerical, and structural changes after development of MDR, alterations in p53 and PTEN, single nucleotide polymorphisms (SNPs) in the mdr1 gene and corresponding protein expression of P-glycoprotein (P-gp) in three human MDR cancer cell lines: non-small cell lung carcinoma NCI-H460/R, colorectal carcinoma DLD1-TxR, and glioma U87-TxR. In addition, we explored how these molecular and phenotypic alterations influence the anticancer effect of new drugs. Cytogenetic analysis showed polyploidy reduction after development of MDR in U87-TxR. Losses of 6q in all resistant cancer cell lines and inactivation of p53 in U87-TxR and PTEN in DLD1-TxR were also revealed. Overexpression of P-gp was observed in all MDR cancer cell lines. We evaluated the anticancer activities and MDR reversal potential of Akt inhibitor GSK690693, Ras inhibitor Tipifarnib, and two P-gp inhibitors (jatrophane diterpenoids). Their effects vary due to the cell-type differences, existence of MDR phenotype, presence of mdr1 SNP, and tumor suppressors' alterations. Tipifarnib and jatrophane diterpenoids significantly sensitized MDR cancer cells to paclitaxel. In conclusion, investigated MDR cancer cells obtained new molecular and cytogenetic characteristics that may serve as potential clinical prognostic markers. In addition, these MDR cancer cell lines present a valuable model for preclinical evaluation of new anticancer agents.
PB  - Springer, New York
T2  - Cancer Chemotherapy and Pharmacology
T1  - Molecular and cytogenetic changes in multi-drug resistant cancer cells and their influence on new compounds testing
VL  - 72
IS  - 3
SP  - 683
EP  - 697
DO  - 10.1007/s00280-013-2247-1
ER  - 

@article{
author = "Podolski-Renic, Ana and Jadranin, Milka and Stankovic, Tijana and Bankovic, Jasna and Stojkovic, Sonja and Chiourea, Maria and Aljančić, Ivana and Vajs, Vlatka and Tešević, Vele and Ruzdijic, Sabera and Gagos, Sarantis and Tanic, Nikola and Pešić, Milica",
year = "2013",
abstract = "Multi-drug resistance (MDR) is a major obstacle to successful cancer treatment. Therefore, in vitro models are necessary for the investigation of the phenotypic changes provoked by cytotoxic agents and more importantly for preclinical testing of new anticancer drugs. We analyzed chromosomal, numerical, and structural changes after development of MDR, alterations in p53 and PTEN, single nucleotide polymorphisms (SNPs) in the mdr1 gene and corresponding protein expression of P-glycoprotein (P-gp) in three human MDR cancer cell lines: non-small cell lung carcinoma NCI-H460/R, colorectal carcinoma DLD1-TxR, and glioma U87-TxR. In addition, we explored how these molecular and phenotypic alterations influence the anticancer effect of new drugs. Cytogenetic analysis showed polyploidy reduction after development of MDR in U87-TxR. Losses of 6q in all resistant cancer cell lines and inactivation of p53 in U87-TxR and PTEN in DLD1-TxR were also revealed. Overexpression of P-gp was observed in all MDR cancer cell lines. We evaluated the anticancer activities and MDR reversal potential of Akt inhibitor GSK690693, Ras inhibitor Tipifarnib, and two P-gp inhibitors (jatrophane diterpenoids). Their effects vary due to the cell-type differences, existence of MDR phenotype, presence of mdr1 SNP, and tumor suppressors' alterations. Tipifarnib and jatrophane diterpenoids significantly sensitized MDR cancer cells to paclitaxel. In conclusion, investigated MDR cancer cells obtained new molecular and cytogenetic characteristics that may serve as potential clinical prognostic markers. In addition, these MDR cancer cell lines present a valuable model for preclinical evaluation of new anticancer agents.",
publisher = "Springer, New York",
journal = "Cancer Chemotherapy and Pharmacology",
title = "Molecular and cytogenetic changes in multi-drug resistant cancer cells and their influence on new compounds testing",
volume = "72",
number = "3",
pages = "683-697",
doi = "10.1007/s00280-013-2247-1"
}

Podolski-Renic, A., Jadranin, M., Stankovic, T., Bankovic, J., Stojkovic, S., Chiourea, M., Aljančić, I., Vajs, V., Tešević, V., Ruzdijic, S., Gagos, S., Tanic, N.,& Pešić, M.. (2013). Molecular and cytogenetic changes in multi-drug resistant cancer cells and their influence on new compounds testing. in Cancer Chemotherapy and Pharmacology
Springer, New York., 72(3), 683-697.
https://doi.org/10.1007/s00280-013-2247-1

Podolski-Renic A, Jadranin M, Stankovic T, Bankovic J, Stojkovic S, Chiourea M, Aljančić I, Vajs V, Tešević V, Ruzdijic S, Gagos S, Tanic N, Pešić M. Molecular and cytogenetic changes in multi-drug resistant cancer cells and their influence on new compounds testing. in Cancer Chemotherapy and Pharmacology. 2013;72(3):683-697.
doi:10.1007/s00280-013-2247-1 .

Podolski-Renic, Ana, Jadranin, Milka, Stankovic, Tijana, Bankovic, Jasna, Stojkovic, Sonja, Chiourea, Maria, Aljančić, Ivana, Vajs, Vlatka, Tešević, Vele, Ruzdijic, Sabera, Gagos, Sarantis, Tanic, Nikola, Pešić, Milica, "Molecular and cytogenetic changes in multi-drug resistant cancer cells and their influence on new compounds testing" in Cancer Chemotherapy and Pharmacology, 72, no. 3 (2013):683-697,
https://doi.org/10.1007/s00280-013-2247-1 . .

TY  - JOUR
AU  - Pešić, Milica
AU  - Bankovic, Jasna
AU  - Aljančić, Ivana
AU  - Todorović, Nina
AU  - Jadranin, Milka
AU  - Vajs, Vlatka
AU  - Tešević, Vele
AU  - Vučković, Ivan
AU  - Momcilovic, Miljana
AU  - Markovic, Ivanka D.
AU  - Tanic, Nikola
AU  - Ruzdijic, Sabera
PY  - 2011
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/830
AB  - Jatrophane diterpenes were shown to be inhibitors of P-glycoprotein (P-gp). There are also evidences on their microtubule-interacting activity in cancer cells. We evaluated new anti-cancer characteristics of two jatrophane type compounds from Euphorbia dendroides. For that purpose, the model system of sensitive non-small cell lung cancer cell line (NCI-H460) and its resistant counterpart (NCI-H460/R) was used. Although both jatrophanes showed inhibitory effect on cancer cell growth, they were non-toxic for peripheral blood mononuclear cells (PBMC). We examined their effects in combination with paclitaxel (PTX), a well-known mitotic spindle interacting chemotherapeutic. Jatrophanes overcome PTX resistance in concentration-dependent manner in MDR cancer cell line (NCI-H460/R). We observed that this synergistic effect is not caused merely by P-gp inhibition. In combination with PTX, jatrophanes induce cell killing and change cell cycle distribution leading to G2/M arrest. Furthermore, they exert an anti-angiogenic effect by decreasing the vascular endothelial growth factor (VEGF) secretion. The reduction of the level of mdr1 mRNA expression in sensitive cells, suggests that these compounds could not contribute to the development of resistance. In conclusion, present study provides a rational basis for the new cancer treatment approach with jatrophanes that are non-toxic to normal cells and have new favorable anti-cancer characteristics.
PB  - Oxford : Pergamon-Elsevier Science Ltd
T2  - Food and Chemical Toxicology
T1  - New anti-cancer characteristics of jatrophane diterpenes from Euphorbia dendroides
VL  - 49
IS  - 12
SP  - 3165
EP  - 3173
DO  - 10.1016/j.fct.2011.09.035
ER  - 

@article{
author = "Pešić, Milica and Bankovic, Jasna and Aljančić, Ivana and Todorović, Nina and Jadranin, Milka and Vajs, Vlatka and Tešević, Vele and Vučković, Ivan and Momcilovic, Miljana and Markovic, Ivanka D. and Tanic, Nikola and Ruzdijic, Sabera",
year = "2011",
abstract = "Jatrophane diterpenes were shown to be inhibitors of P-glycoprotein (P-gp). There are also evidences on their microtubule-interacting activity in cancer cells. We evaluated new anti-cancer characteristics of two jatrophane type compounds from Euphorbia dendroides. For that purpose, the model system of sensitive non-small cell lung cancer cell line (NCI-H460) and its resistant counterpart (NCI-H460/R) was used. Although both jatrophanes showed inhibitory effect on cancer cell growth, they were non-toxic for peripheral blood mononuclear cells (PBMC). We examined their effects in combination with paclitaxel (PTX), a well-known mitotic spindle interacting chemotherapeutic. Jatrophanes overcome PTX resistance in concentration-dependent manner in MDR cancer cell line (NCI-H460/R). We observed that this synergistic effect is not caused merely by P-gp inhibition. In combination with PTX, jatrophanes induce cell killing and change cell cycle distribution leading to G2/M arrest. Furthermore, they exert an anti-angiogenic effect by decreasing the vascular endothelial growth factor (VEGF) secretion. The reduction of the level of mdr1 mRNA expression in sensitive cells, suggests that these compounds could not contribute to the development of resistance. In conclusion, present study provides a rational basis for the new cancer treatment approach with jatrophanes that are non-toxic to normal cells and have new favorable anti-cancer characteristics.",
publisher = "Oxford : Pergamon-Elsevier Science Ltd",
journal = "Food and Chemical Toxicology",
title = "New anti-cancer characteristics of jatrophane diterpenes from Euphorbia dendroides",
volume = "49",
number = "12",
pages = "3165-3173",
doi = "10.1016/j.fct.2011.09.035"
}

Pešić, M., Bankovic, J., Aljančić, I., Todorović, N., Jadranin, M., Vajs, V., Tešević, V., Vučković, I., Momcilovic, M., Markovic, I. D., Tanic, N.,& Ruzdijic, S.. (2011). New anti-cancer characteristics of jatrophane diterpenes from Euphorbia dendroides. in Food and Chemical Toxicology
Oxford : Pergamon-Elsevier Science Ltd., 49(12), 3165-3173.
https://doi.org/10.1016/j.fct.2011.09.035

Pešić M, Bankovic J, Aljančić I, Todorović N, Jadranin M, Vajs V, Tešević V, Vučković I, Momcilovic M, Markovic ID, Tanic N, Ruzdijic S. New anti-cancer characteristics of jatrophane diterpenes from Euphorbia dendroides. in Food and Chemical Toxicology. 2011;49(12):3165-3173.
doi:10.1016/j.fct.2011.09.035 .

Pešić, Milica, Bankovic, Jasna, Aljančić, Ivana, Todorović, Nina, Jadranin, Milka, Vajs, Vlatka, Tešević, Vele, Vučković, Ivan, Momcilovic, Miljana, Markovic, Ivanka D., Tanic, Nikola, Ruzdijic, Sabera, "New anti-cancer characteristics of jatrophane diterpenes from Euphorbia dendroides" in Food and Chemical Toxicology, 49, no. 12 (2011):3165-3173,
https://doi.org/10.1016/j.fct.2011.09.035 . .