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  - 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  - Popović, Marjan
AU  - Stanojević, Željka
AU  - Tosic, Jelena
AU  - Isaković, Aleksandra
AU  - Paunović, Verica
AU  - Petricevic, Sasa
AU  - Martinović, Tamara
AU  - Ciric, Darko
AU  - Kravić-Stevović, Tamara
AU  - Šoškić, Vukić
AU  - Kostić Rajačić, Slađana
AU  - Shakib, Kaveh
AU  - Bumbasirevic, Vladimir
AU  - Trajković, Vladimir
PY  - 2015
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1812
AB  - Arylpiperazine-based dopaminergic/serotonergic ligands exert neuroprotective activity. We examined the effect of arylpiperazine D-2/5-HT1A ligands, N-{4-[2-(4-phenyl-piperazin-1-yl)-ethyl}-phenyl]- picolinamide (6a) and N-{3-[2-(4-phenyl-piperazin-1-yl)ethyl]- phenyl}-picolinamide (6b), in experimental autoimmune encephalomyelitis (EAE), a model of neuroinflammation. Both compounds (10 mg/kg i.p.) reduced EAE clinical signs in spinal cord homogenate-immunized Dark Agouti rats. Compound 6b was more efficient in delaying the disease onset and reducing the maximal clinical score, which correlated with its higher affinity for D-2 and 5-HT1A receptors. The protectionwas retainedif treatment was limited to the effector (from day 8 onwards), but not the induction phase (day 0-7) of EAE. Compound 6b reduced CNS immune infiltration and expression of mRNA encoding the proinflammatory cytokines tumor necrosis factor, IL-6, IL-1, and GM-CSF, T(H)1 cytokine IFN-gamma, T(H)17 cytokine IL-17, as well as the signature transcription factors of T(H)1 (T-bet) and T(H)17 (ROR gamma t) cells. Arylpiperazine treatment reduced apoptosis and increased the activation of anti-apoptotic mediators Akt and p70S6 kinase in the CNS of EAE animals. The in vitro treatment with 6b protected oligodendrocyte cell line OLN-93 and neuronal cell line PC12 from mitogen-activated normal T cells or myelin basic proteinactivated encephalitogenic T cells. In conclusion, arylpiperazine dopaminergic/serotonergic ligands suppress EAE through a direct neuroprotective action and decrease inCNS inflammation.
PB  - Wiley, Hoboken
T2  - Journal of Neurochemistry
T1  - Neuroprotective arylpiperazine dopaminergic/serotonergic ligands suppress experimental autoimmune encephalomyelitis in rats
VL  - 135
IS  - 1
SP  - 125
EP  - 138
DO  - 10.1111/jnc.13198
ER  - 

@article{
author = "Popović, Marjan and Stanojević, Željka and Tosic, Jelena and Isaković, Aleksandra and Paunović, Verica and Petricevic, Sasa and Martinović, Tamara and Ciric, Darko and Kravić-Stevović, Tamara and Šoškić, Vukić and Kostić Rajačić, Slađana and Shakib, Kaveh and Bumbasirevic, Vladimir and Trajković, Vladimir",
year = "2015",
abstract = "Arylpiperazine-based dopaminergic/serotonergic ligands exert neuroprotective activity. We examined the effect of arylpiperazine D-2/5-HT1A ligands, N-{4-[2-(4-phenyl-piperazin-1-yl)-ethyl}-phenyl]- picolinamide (6a) and N-{3-[2-(4-phenyl-piperazin-1-yl)ethyl]- phenyl}-picolinamide (6b), in experimental autoimmune encephalomyelitis (EAE), a model of neuroinflammation. Both compounds (10 mg/kg i.p.) reduced EAE clinical signs in spinal cord homogenate-immunized Dark Agouti rats. Compound 6b was more efficient in delaying the disease onset and reducing the maximal clinical score, which correlated with its higher affinity for D-2 and 5-HT1A receptors. The protectionwas retainedif treatment was limited to the effector (from day 8 onwards), but not the induction phase (day 0-7) of EAE. Compound 6b reduced CNS immune infiltration and expression of mRNA encoding the proinflammatory cytokines tumor necrosis factor, IL-6, IL-1, and GM-CSF, T(H)1 cytokine IFN-gamma, T(H)17 cytokine IL-17, as well as the signature transcription factors of T(H)1 (T-bet) and T(H)17 (ROR gamma t) cells. Arylpiperazine treatment reduced apoptosis and increased the activation of anti-apoptotic mediators Akt and p70S6 kinase in the CNS of EAE animals. The in vitro treatment with 6b protected oligodendrocyte cell line OLN-93 and neuronal cell line PC12 from mitogen-activated normal T cells or myelin basic proteinactivated encephalitogenic T cells. In conclusion, arylpiperazine dopaminergic/serotonergic ligands suppress EAE through a direct neuroprotective action and decrease inCNS inflammation.",
publisher = "Wiley, Hoboken",
journal = "Journal of Neurochemistry",
title = "Neuroprotective arylpiperazine dopaminergic/serotonergic ligands suppress experimental autoimmune encephalomyelitis in rats",
volume = "135",
number = "1",
pages = "125-138",
doi = "10.1111/jnc.13198"
}

Popović, M., Stanojević, Ž., Tosic, J., Isaković, A., Paunović, V., Petricevic, S., Martinović, T., Ciric, D., Kravić-Stevović, T., Šoškić, V., Kostić Rajačić, S., Shakib, K., Bumbasirevic, V.,& Trajković, V.. (2015). Neuroprotective arylpiperazine dopaminergic/serotonergic ligands suppress experimental autoimmune encephalomyelitis in rats. in Journal of Neurochemistry
Wiley, Hoboken., 135(1), 125-138.
https://doi.org/10.1111/jnc.13198

Popović M, Stanojević Ž, Tosic J, Isaković A, Paunović V, Petricevic S, Martinović T, Ciric D, Kravić-Stevović T, Šoškić V, Kostić Rajačić S, Shakib K, Bumbasirevic V, Trajković V. Neuroprotective arylpiperazine dopaminergic/serotonergic ligands suppress experimental autoimmune encephalomyelitis in rats. in Journal of Neurochemistry. 2015;135(1):125-138.
doi:10.1111/jnc.13198 .

Popović, Marjan, Stanojević, Željka, Tosic, Jelena, Isaković, Aleksandra, Paunović, Verica, Petricevic, Sasa, Martinović, Tamara, Ciric, Darko, Kravić-Stevović, Tamara, Šoškić, Vukić, Kostić Rajačić, Slađana, Shakib, Kaveh, Bumbasirevic, Vladimir, Trajković, Vladimir, "Neuroprotective arylpiperazine dopaminergic/serotonergic ligands suppress experimental autoimmune encephalomyelitis in rats" in Journal of Neurochemistry, 135, no. 1 (2015):125-138,
https://doi.org/10.1111/jnc.13198 . .

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  - Trifunović, Snežana
AU  - Isaković, Anđelka M.
AU  - Isaković, Aleksandra
AU  - Vučković, Ivan
AU  - Mandić, Boris
AU  - Novaković, Miroslav
AU  - Vajs, Vlatka
AU  - Milosavljević, Slobodan
AU  - Trajković, Vladimir
PY  - 2014
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3120
AB  - Further phytochemical investigation into the aerial parts of Achillea clavennae has resulted in the 3 isolation of three new sesquiterpene lactones: two highly oxygenated germacranolides (1, 2) and 4 the iso-seco-guaianolide, 9(R)-acetoxy-3-O-methyl-iso-seco-tanapartholide (3). Eight known 5 compounds were also found in this plant species, of which 9 α -acetoxycanin (5), sintenin (6) and 6 oleanolic acid (7) were detected for the first time. The structures of the isolated compounds were 7 elucidated by combined spectroscopic methods (1D and 2D NMR, HRESIMS, CIMS, FTIR). 8 While the predominant metabolite germacranolide sintenin (6) was not cytotoxic, the new iso-9 seco-guaianolide (3) displayed cytotoxicity comparable to that of cisplatin and the lactone 10 apressin (4), inducing partly apoptotic death in human U251 and rat C6 glioma cell lines.
PB  - Georg Thieme Verlag
T2  - Planta medica
T1  - Isolation, characterization and in vitro cytotoxicity of new sesquiterpenoids from Achillea clavennae
VL  - 80
IS  - 4
SP  - 275
EP  - 305
DO  - 10.1055/s-0033-1360312
ER  - 

@article{
author = "Trifunović, Snežana and Isaković, Anđelka M. and Isaković, Aleksandra and Vučković, Ivan and Mandić, Boris and Novaković, Miroslav and Vajs, Vlatka and Milosavljević, Slobodan and Trajković, Vladimir",
year = "2014",
abstract = "Further phytochemical investigation into the aerial parts of Achillea clavennae has resulted in the 3 isolation of three new sesquiterpene lactones: two highly oxygenated germacranolides (1, 2) and 4 the iso-seco-guaianolide, 9(R)-acetoxy-3-O-methyl-iso-seco-tanapartholide (3). Eight known 5 compounds were also found in this plant species, of which 9 α -acetoxycanin (5), sintenin (6) and 6 oleanolic acid (7) were detected for the first time. The structures of the isolated compounds were 7 elucidated by combined spectroscopic methods (1D and 2D NMR, HRESIMS, CIMS, FTIR). 8 While the predominant metabolite germacranolide sintenin (6) was not cytotoxic, the new iso-9 seco-guaianolide (3) displayed cytotoxicity comparable to that of cisplatin and the lactone 10 apressin (4), inducing partly apoptotic death in human U251 and rat C6 glioma cell lines.",
publisher = "Georg Thieme Verlag",
journal = "Planta medica",
title = "Isolation, characterization and in vitro cytotoxicity of new sesquiterpenoids from Achillea clavennae",
volume = "80",
number = "4",
pages = "275-305",
doi = "10.1055/s-0033-1360312"
}

Trifunović, S., Isaković, A. M., Isaković, A., Vučković, I., Mandić, B., Novaković, M., Vajs, V., Milosavljević, S.,& Trajković, V.. (2014). Isolation, characterization and in vitro cytotoxicity of new sesquiterpenoids from Achillea clavennae. in Planta medica
Georg Thieme Verlag., 80(4), 275-305.
https://doi.org/10.1055/s-0033-1360312

Trifunović S, Isaković AM, Isaković A, Vučković I, Mandić B, Novaković M, Vajs V, Milosavljević S, Trajković V. Isolation, characterization and in vitro cytotoxicity of new sesquiterpenoids from Achillea clavennae. in Planta medica. 2014;80(4):275-305.
doi:10.1055/s-0033-1360312 .

Trifunović, Snežana, Isaković, Anđelka M., Isaković, Aleksandra, Vučković, Ivan, Mandić, Boris, Novaković, Miroslav, Vajs, Vlatka, Milosavljević, Slobodan, Trajković, Vladimir, "Isolation, characterization and in vitro cytotoxicity of new sesquiterpenoids from Achillea clavennae" in Planta medica, 80, no. 4 (2014):275-305,
https://doi.org/10.1055/s-0033-1360312 . .

TY  - JOUR
AU  - Trifunović, Snežana
AU  - Isaković, Anđelka M.
AU  - Isaković, Aleksandra
AU  - Vučković, Ivan
AU  - Mandić, Boris
AU  - Novaković, Miroslav
AU  - Vajs, Vlatka
AU  - Milosavljević, Slobodan
AU  - Trajković, Vladimir
PY  - 2014
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1534
AB  - Further phytochemical investigation of the aerial parts of Achillea clavennae has resulted in the isolation of three new sesquiterpene lactones: two highly oxygenated germacranolides (1, 2) and the iso-seco-guaianolide 9(R)-acetoxy-3-O-methyl-iso-seco-tanapartholide (3). Eight known compounds were also found, of which 9-acetoxycanin (5), sintenin (6), and oleanolic acid (7) were detected for the first time. The structures of the isolated compounds were elucidated by combined spectroscopic methods (1D and 2DNMR, HRESIMS, CIMS, and FTIR). While the predominant metabolite germacranolide sintenin (6) was not cytotoxic, the new iso-seco-guaianolide (3) displayed cytotoxicity comparable to that of cisplatin and the lactone apressin (4), inducing partly apoptotic death in human U251 and rat C6 glioma cell lines.
PB  - Georg Thieme Verlag Kg, Stuttgart
T2  - Planta Medica
T1  - Isolation, Characterization, and In Vitro Cytotoxicity of New Sesquiterpenoids from Achillea clavennae
VL  - 80
IS  - 4
SP  - 297
EP  - 305
DO  - 10.1055/s-0033-1360312
ER  - 

@article{
author = "Trifunović, Snežana and Isaković, Anđelka M. and Isaković, Aleksandra and Vučković, Ivan and Mandić, Boris and Novaković, Miroslav and Vajs, Vlatka and Milosavljević, Slobodan and Trajković, Vladimir",
year = "2014",
abstract = "Further phytochemical investigation of the aerial parts of Achillea clavennae has resulted in the isolation of three new sesquiterpene lactones: two highly oxygenated germacranolides (1, 2) and the iso-seco-guaianolide 9(R)-acetoxy-3-O-methyl-iso-seco-tanapartholide (3). Eight known compounds were also found, of which 9-acetoxycanin (5), sintenin (6), and oleanolic acid (7) were detected for the first time. The structures of the isolated compounds were elucidated by combined spectroscopic methods (1D and 2DNMR, HRESIMS, CIMS, and FTIR). While the predominant metabolite germacranolide sintenin (6) was not cytotoxic, the new iso-seco-guaianolide (3) displayed cytotoxicity comparable to that of cisplatin and the lactone apressin (4), inducing partly apoptotic death in human U251 and rat C6 glioma cell lines.",
publisher = "Georg Thieme Verlag Kg, Stuttgart",
journal = "Planta Medica",
title = "Isolation, Characterization, and In Vitro Cytotoxicity of New Sesquiterpenoids from Achillea clavennae",
volume = "80",
number = "4",
pages = "297-305",
doi = "10.1055/s-0033-1360312"
}

Trifunović, S., Isaković, A. M., Isaković, A., Vučković, I., Mandić, B., Novaković, M., Vajs, V., Milosavljević, S.,& Trajković, V.. (2014). Isolation, Characterization, and In Vitro Cytotoxicity of New Sesquiterpenoids from Achillea clavennae. in Planta Medica
Georg Thieme Verlag Kg, Stuttgart., 80(4), 297-305.
https://doi.org/10.1055/s-0033-1360312

Trifunović S, Isaković AM, Isaković A, Vučković I, Mandić B, Novaković M, Vajs V, Milosavljević S, Trajković V. Isolation, Characterization, and In Vitro Cytotoxicity of New Sesquiterpenoids from Achillea clavennae. in Planta Medica. 2014;80(4):297-305.
doi:10.1055/s-0033-1360312 .

Trifunović, Snežana, Isaković, Anđelka M., Isaković, Aleksandra, Vučković, Ivan, Mandić, Boris, Novaković, Miroslav, Vajs, Vlatka, Milosavljević, Slobodan, Trajković, Vladimir, "Isolation, Characterization, and In Vitro Cytotoxicity of New Sesquiterpenoids from Achillea clavennae" in Planta Medica, 80, no. 4 (2014):297-305,
https://doi.org/10.1055/s-0033-1360312 . .

TY  - JOUR
AU  - Tovilović, Gordana
AU  - Zogovic, Nevena
AU  - Harhaji-Trajković, Ljubica
AU  - Misirkić-Marjanović, Maja
AU  - Janjetovic, Kristina
AU  - Vucicevic, Ljubica
AU  - Kostić Rajačić, Slađana
AU  - Schrattenholz, Andre
AU  - Isaković, Aleksandra
AU  - Šoškić, Vukić
AU  - Trajković, Vladimir
PY  - 2012
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1037
AB  - The protective ability of novel arylpiperazine-based dopaminergic ligands against nitric oxide (NO)-mediated neurotoxicity is investigated. The most potent neuroprotective arylpiperazine identified during the study was N-{4-[2-(4-phenyl-piperazin-1-yl)ethyl]-phenyl}picolinamide, which protected SH-SY5Y human neuron-like cells from the proapoptotic effect of NO donor sodium nitroprusside (SNP) by decreasing oxidative stress, mitochondrial membrane depolarization, caspase activation and subsequent phosphatydilserine externalization/DNA fragmentation. The protective effect was associated with the inhibition of proapoptotic (JNK, ERK, AMPK) and activation of antiapoptotic (Akt) signaling pathways, in the absence of interference with intracellular NO accumulation. The neuroprotective action of arylpiperazines was shown to be independent of dopamine receptor binding, as it was not affected by the high-affinity D1/D2 receptor blocker butaclamol. These results reported support the further study of arylpiperazines as potential neuroprotective agents.
PB  - Wiley-V C H Verlag Gmbh, Weinheim
T2  - Chemmedchem
T1  - Arylpiperazine Dopamineric Ligands Protect Neuroblastoma Cells from Nitric Oxide (NO)-Induced Mitochondrial Damage and Apoptosis
VL  - 7
IS  - 3
SP  - 495
EP  - 508
DO  - 10.1002/cmdc.201100537
ER  - 

@article{
author = "Tovilović, Gordana and Zogovic, Nevena and Harhaji-Trajković, Ljubica and Misirkić-Marjanović, Maja and Janjetovic, Kristina and Vucicevic, Ljubica and Kostić Rajačić, Slađana and Schrattenholz, Andre and Isaković, Aleksandra and Šoškić, Vukić and Trajković, Vladimir",
year = "2012",
abstract = "The protective ability of novel arylpiperazine-based dopaminergic ligands against nitric oxide (NO)-mediated neurotoxicity is investigated. The most potent neuroprotective arylpiperazine identified during the study was N-{4-[2-(4-phenyl-piperazin-1-yl)ethyl]-phenyl}picolinamide, which protected SH-SY5Y human neuron-like cells from the proapoptotic effect of NO donor sodium nitroprusside (SNP) by decreasing oxidative stress, mitochondrial membrane depolarization, caspase activation and subsequent phosphatydilserine externalization/DNA fragmentation. The protective effect was associated with the inhibition of proapoptotic (JNK, ERK, AMPK) and activation of antiapoptotic (Akt) signaling pathways, in the absence of interference with intracellular NO accumulation. The neuroprotective action of arylpiperazines was shown to be independent of dopamine receptor binding, as it was not affected by the high-affinity D1/D2 receptor blocker butaclamol. These results reported support the further study of arylpiperazines as potential neuroprotective agents.",
publisher = "Wiley-V C H Verlag Gmbh, Weinheim",
journal = "Chemmedchem",
title = "Arylpiperazine Dopamineric Ligands Protect Neuroblastoma Cells from Nitric Oxide (NO)-Induced Mitochondrial Damage and Apoptosis",
volume = "7",
number = "3",
pages = "495-508",
doi = "10.1002/cmdc.201100537"
}

Tovilović, G., Zogovic, N., Harhaji-Trajković, L., Misirkić-Marjanović, M., Janjetovic, K., Vucicevic, L., Kostić Rajačić, S., Schrattenholz, A., Isaković, A., Šoškić, V.,& Trajković, V.. (2012). Arylpiperazine Dopamineric Ligands Protect Neuroblastoma Cells from Nitric Oxide (NO)-Induced Mitochondrial Damage and Apoptosis. in Chemmedchem
Wiley-V C H Verlag Gmbh, Weinheim., 7(3), 495-508.
https://doi.org/10.1002/cmdc.201100537

Tovilović G, Zogovic N, Harhaji-Trajković L, Misirkić-Marjanović M, Janjetovic K, Vucicevic L, Kostić Rajačić S, Schrattenholz A, Isaković A, Šoškić V, Trajković V. Arylpiperazine Dopamineric Ligands Protect Neuroblastoma Cells from Nitric Oxide (NO)-Induced Mitochondrial Damage and Apoptosis. in Chemmedchem. 2012;7(3):495-508.
doi:10.1002/cmdc.201100537 .

Tovilović, Gordana, Zogovic, Nevena, Harhaji-Trajković, Ljubica, Misirkić-Marjanović, Maja, Janjetovic, Kristina, Vucicevic, Ljubica, Kostić Rajačić, Slađana, Schrattenholz, Andre, Isaković, Aleksandra, Šoškić, Vukić, Trajković, Vladimir, "Arylpiperazine Dopamineric Ligands Protect Neuroblastoma Cells from Nitric Oxide (NO)-Induced Mitochondrial Damage and Apoptosis" in Chemmedchem, 7, no. 3 (2012):495-508,
https://doi.org/10.1002/cmdc.201100537 . .

TY  - JOUR
AU  - Isaković, Aleksandra
AU  - Janković, Teodora
AU  - Harhaji, Ljubica
AU  - Kostić Rajačić, Slađana
AU  - Nikolić, Zoran
AU  - Vajs, Vlatka
AU  - Trajković, Vladimir
PY  - 2008
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/478
AB  - The present study identifies xanthones gentiakochianin and gentiacaulein as the active principles responsible for the in vitro antiglioma action of ether and methanolic extracts of the plant Gentiana kochiana. Gentiakochianin and gentiacaulein induced cell cycle arrest in G2/M and G0/G1 phases, respectively, in both C6 rat glioma and U251 human glioma cell lines. The more efficient antiproliferative action of gentiakochianin was associated with its ability to induce microtubule stabilization in a cell-free assay. Both the xanthones reduced mitochondrial membrane potential and increased the production of reactive oxygen species in glioma cells, but only the effects of gentiakochianin were pronounced enough to cause caspase activation and subsequent apoptotic cell death. The assessment of structure-activity relationship in a series of structurally related xanthones from G. kochiana and Gentianella austriaca revealed dihydroxylation at positions 7, 8 of the xanthonic nucleus as the key structural feature responsible for the ability of gentiakochianin to induce microtubule-associated G2/M cell block and apoptotic cell death in glioma cells.
PB  - Oxford : Pergamon-Elsevier Science Ltd
T2  - Bioorganic and Medicinal Chemistry
T1  - Antiglioma action of xanthones from Gentiana kochiana: Mechanistic and structure-activity requirements
VL  - 16
IS  - 10
SP  - 5683
EP  - 5694
DO  - 10.1016/j.bmc.2008.03.069
ER  - 

@article{
author = "Isaković, Aleksandra and Janković, Teodora and Harhaji, Ljubica and Kostić Rajačić, Slađana and Nikolić, Zoran and Vajs, Vlatka and Trajković, Vladimir",
year = "2008",
abstract = "The present study identifies xanthones gentiakochianin and gentiacaulein as the active principles responsible for the in vitro antiglioma action of ether and methanolic extracts of the plant Gentiana kochiana. Gentiakochianin and gentiacaulein induced cell cycle arrest in G2/M and G0/G1 phases, respectively, in both C6 rat glioma and U251 human glioma cell lines. The more efficient antiproliferative action of gentiakochianin was associated with its ability to induce microtubule stabilization in a cell-free assay. Both the xanthones reduced mitochondrial membrane potential and increased the production of reactive oxygen species in glioma cells, but only the effects of gentiakochianin were pronounced enough to cause caspase activation and subsequent apoptotic cell death. The assessment of structure-activity relationship in a series of structurally related xanthones from G. kochiana and Gentianella austriaca revealed dihydroxylation at positions 7, 8 of the xanthonic nucleus as the key structural feature responsible for the ability of gentiakochianin to induce microtubule-associated G2/M cell block and apoptotic cell death in glioma cells.",
publisher = "Oxford : Pergamon-Elsevier Science Ltd",
journal = "Bioorganic and Medicinal Chemistry",
title = "Antiglioma action of xanthones from Gentiana kochiana: Mechanistic and structure-activity requirements",
volume = "16",
number = "10",
pages = "5683-5694",
doi = "10.1016/j.bmc.2008.03.069"
}

Isaković, A., Janković, T., Harhaji, L., Kostić Rajačić, S., Nikolić, Z., Vajs, V.,& Trajković, V.. (2008). Antiglioma action of xanthones from Gentiana kochiana: Mechanistic and structure-activity requirements. in Bioorganic and Medicinal Chemistry
Oxford : Pergamon-Elsevier Science Ltd., 16(10), 5683-5694.
https://doi.org/10.1016/j.bmc.2008.03.069

Isaković A, Janković T, Harhaji L, Kostić Rajačić S, Nikolić Z, Vajs V, Trajković V. Antiglioma action of xanthones from Gentiana kochiana: Mechanistic and structure-activity requirements. in Bioorganic and Medicinal Chemistry. 2008;16(10):5683-5694.
doi:10.1016/j.bmc.2008.03.069 .

Isaković, Aleksandra, Janković, Teodora, Harhaji, Ljubica, Kostić Rajačić, Slađana, Nikolić, Zoran, Vajs, Vlatka, Trajković, Vladimir, "Antiglioma action of xanthones from Gentiana kochiana: Mechanistic and structure-activity requirements" in Bioorganic and Medicinal Chemistry, 16, no. 10 (2008):5683-5694,
https://doi.org/10.1016/j.bmc.2008.03.069 . .

TY  - JOUR
AU  - Isaković, Aleksandra
AU  - Marković, Zoran M.
AU  - Nikolić, Nadežda
AU  - Todorović-Marković, Biljana
AU  - Vranješ-Đurić, Sanja
AU  - Harhaji, Ljubica
AU  - Raičević, Nevena
AU  - Romčević, Nebojša
AU  - Vasiljević-Radović, Dana
AU  - Dramićanin, Miroslav
AU  - Trajković, Vladimir
PY  - 2006
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4120
AB  - We investigated the effect of γ-irradiation on the cytotoxicity of pure C 60 solubilized in water by using tetrahydrofuran (THF/n-C 60 or THF/n-C 60 ). In contrast to THF/n-C 60 , its γ-irradiated counterpart failed to generate oxygen radicals and cause extracellular signal-regulated kinase (ERK)-dependent necrotic cell death in various types of mammalian cells. Moreover, γ-irradiated THF/n-C 60 protected cells from the oxidative stress induced by native THF/n-C 60 or hydrogen peroxide. The observed biological effects were associated with γ-irradiation-mediated decomposition of THF and subsequent derivatization of the n-C 60 surface. These results for the first time demonstrate γ-irradiation-mediated changes in the physico-chemical properties of THF-prepared nanocrystalline C 60 , resulting in a complete loss of its cytotoxic effect and its conversion to a cytoprotective agent.
PB  - Elsevier
T2  - Biomaterials
T1  - Inactivation of nanocrystalline C60 cytotoxicity by γ-irradiation
VL  - 27
IS  - 29
SP  - 5049
EP  - 5058
DO  - 10.1016/j.biomaterials.2006.05.047
ER  - 

@article{
author = "Isaković, Aleksandra and Marković, Zoran M. and Nikolić, Nadežda and Todorović-Marković, Biljana and Vranješ-Đurić, Sanja and Harhaji, Ljubica and Raičević, Nevena and Romčević, Nebojša and Vasiljević-Radović, Dana and Dramićanin, Miroslav and Trajković, Vladimir",
year = "2006",
abstract = "We investigated the effect of γ-irradiation on the cytotoxicity of pure C 60 solubilized in water by using tetrahydrofuran (THF/n-C 60 or THF/n-C 60 ). In contrast to THF/n-C 60 , its γ-irradiated counterpart failed to generate oxygen radicals and cause extracellular signal-regulated kinase (ERK)-dependent necrotic cell death in various types of mammalian cells. Moreover, γ-irradiated THF/n-C 60 protected cells from the oxidative stress induced by native THF/n-C 60 or hydrogen peroxide. The observed biological effects were associated with γ-irradiation-mediated decomposition of THF and subsequent derivatization of the n-C 60 surface. These results for the first time demonstrate γ-irradiation-mediated changes in the physico-chemical properties of THF-prepared nanocrystalline C 60 , resulting in a complete loss of its cytotoxic effect and its conversion to a cytoprotective agent.",
publisher = "Elsevier",
journal = "Biomaterials",
title = "Inactivation of nanocrystalline C60 cytotoxicity by γ-irradiation",
volume = "27",
number = "29",
pages = "5049-5058",
doi = "10.1016/j.biomaterials.2006.05.047"
}

Isaković, A., Marković, Z. M., Nikolić, N., Todorović-Marković, B., Vranješ-Đurić, S., Harhaji, L., Raičević, N., Romčević, N., Vasiljević-Radović, D., Dramićanin, M.,& Trajković, V.. (2006). Inactivation of nanocrystalline C60 cytotoxicity by γ-irradiation. in Biomaterials
Elsevier., 27(29), 5049-5058.
https://doi.org/10.1016/j.biomaterials.2006.05.047

Isaković A, Marković ZM, Nikolić N, Todorović-Marković B, Vranješ-Đurić S, Harhaji L, Raičević N, Romčević N, Vasiljević-Radović D, Dramićanin M, Trajković V. Inactivation of nanocrystalline C60 cytotoxicity by γ-irradiation. in Biomaterials. 2006;27(29):5049-5058.
doi:10.1016/j.biomaterials.2006.05.047 .

Isaković, Aleksandra, Marković, Zoran M., Nikolić, Nadežda, Todorović-Marković, Biljana, Vranješ-Đurić, Sanja, Harhaji, Ljubica, Raičević, Nevena, Romčević, Nebojša, Vasiljević-Radović, Dana, Dramićanin, Miroslav, Trajković, Vladimir, "Inactivation of nanocrystalline C60 cytotoxicity by γ-irradiation" in Biomaterials, 27, no. 29 (2006):5049-5058,
https://doi.org/10.1016/j.biomaterials.2006.05.047 . .