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  - 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  - 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  - 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 . .