TY  - JOUR
AU  - Hicke, Francisco J.
AU  - Puerta, Adrián
AU  - Dinić, Jelena
AU  - Pešić, Milica
AU  - Padrón, José M.
AU  - López, Óscar
AU  - Fernández-Bolaños, José G.
PY  - 2022
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/4869
AB  - The necessity for developing novel cytostatic agents with improved activities and reduced side-effects to tackle cancer prompted us to investigate mitochondria-targeted compounds, an approach that is gaining attention for the selective transportation of cytotoxic agents. We envisioned the possibility of conjugating a phenethyl alcohol motif, decorated with a series of phenol-based substituents on the aryl moiety, with a triphenyl phosphonium scaffold (a mitochondria-directed vector), through a hydrocarbon chain of different lengths. Thus, such compounds that incorporate the phenethyl skeleton can be considered as masked phenolic compounds derived from relevant natural counterparts found in olive tree (e.g. tyrosol, hydroxytyrosol). Title compounds exhibited very strong in vitro antiproliferative activities against the panel of six human tumor cell lines tested, with GI50 values ranging from the nanomolar (0.026 ± 0.010 μM for 36) to the submicromolar range in most of the cases; this represents an improvement of up to 350-fold compared to classical chemotherapeutic agents, like 5-fluorouracil or cisplatin. Interestingly, decrease in the linker length led to an increase of GI50 values against non-tumor cells, thus allowing a remarkable improvement of selectivity (SI up to 269). The very promising antiproliferative activities prompted us to further investigate their behaviour against multidrug resistant cell lines (MDR). The results indicated a reduced sensitivity of the multidrug resistant cells to compounds, probably due to P-gp-mediated efflux of these antiproliferative agents. Interestingly, activities were completely restored to the same levels by co-administration of tariquidar, a well-known inhibitor of P-gp. Flow cytometry analysis on sensitive cell lines revealed a decrease in the percentage of cells in G1 phase accompanied by increase in S and G2/M phases. In addition, a significant increase in subG1 area, was observed. These results are compatible with the necrotic and apoptotic cell death detected in the Annexin V assay, and with the depolarization of the mitochondria membrane. Thus, the new mitochondriotropic agents reported herein can be considered as promising antiproliferative agents, endowed with remarkable potency and selectivity, including MDR cells, upon co-administration with a pump-efflux inhibitor.
PB  - Elsevier
T2  - European Journal of Medicinal Chemistry
T1  - Straightforward access to novel mitochondriotropics derived from 2-arylethanol as potent and selective antiproliferative agents
VL  - 228
SP  - 113980
DO  - 10.1016/j.ejmech.2021.113980
ER  - 

@article{
author = "Hicke, Francisco J. and Puerta, Adrián and Dinić, Jelena and Pešić, Milica and Padrón, José M. and López, Óscar and Fernández-Bolaños, José G.",
year = "2022",
abstract = "The necessity for developing novel cytostatic agents with improved activities and reduced side-effects to tackle cancer prompted us to investigate mitochondria-targeted compounds, an approach that is gaining attention for the selective transportation of cytotoxic agents. We envisioned the possibility of conjugating a phenethyl alcohol motif, decorated with a series of phenol-based substituents on the aryl moiety, with a triphenyl phosphonium scaffold (a mitochondria-directed vector), through a hydrocarbon chain of different lengths. Thus, such compounds that incorporate the phenethyl skeleton can be considered as masked phenolic compounds derived from relevant natural counterparts found in olive tree (e.g. tyrosol, hydroxytyrosol). Title compounds exhibited very strong in vitro antiproliferative activities against the panel of six human tumor cell lines tested, with GI50 values ranging from the nanomolar (0.026 ± 0.010 μM for 36) to the submicromolar range in most of the cases; this represents an improvement of up to 350-fold compared to classical chemotherapeutic agents, like 5-fluorouracil or cisplatin. Interestingly, decrease in the linker length led to an increase of GI50 values against non-tumor cells, thus allowing a remarkable improvement of selectivity (SI up to 269). The very promising antiproliferative activities prompted us to further investigate their behaviour against multidrug resistant cell lines (MDR). The results indicated a reduced sensitivity of the multidrug resistant cells to compounds, probably due to P-gp-mediated efflux of these antiproliferative agents. Interestingly, activities were completely restored to the same levels by co-administration of tariquidar, a well-known inhibitor of P-gp. Flow cytometry analysis on sensitive cell lines revealed a decrease in the percentage of cells in G1 phase accompanied by increase in S and G2/M phases. In addition, a significant increase in subG1 area, was observed. These results are compatible with the necrotic and apoptotic cell death detected in the Annexin V assay, and with the depolarization of the mitochondria membrane. Thus, the new mitochondriotropic agents reported herein can be considered as promising antiproliferative agents, endowed with remarkable potency and selectivity, including MDR cells, upon co-administration with a pump-efflux inhibitor.",
publisher = "Elsevier",
journal = "European Journal of Medicinal Chemistry",
title = "Straightforward access to novel mitochondriotropics derived from 2-arylethanol as potent and selective antiproliferative agents",
volume = "228",
pages = "113980",
doi = "10.1016/j.ejmech.2021.113980"
}

Hicke, F. J., Puerta, A., Dinić, J., Pešić, M., Padrón, J. M., López, Ó.,& Fernández-Bolaños, J. G.. (2022). Straightforward access to novel mitochondriotropics derived from 2-arylethanol as potent and selective antiproliferative agents. in European Journal of Medicinal Chemistry
Elsevier., 228, 113980.
https://doi.org/10.1016/j.ejmech.2021.113980

Hicke FJ, Puerta A, Dinić J, Pešić M, Padrón JM, López Ó, Fernández-Bolaños JG. Straightforward access to novel mitochondriotropics derived from 2-arylethanol as potent and selective antiproliferative agents. in European Journal of Medicinal Chemistry. 2022;228:113980.
doi:10.1016/j.ejmech.2021.113980 .

Hicke, Francisco J., Puerta, Adrián, Dinić, Jelena, Pešić, Milica, Padrón, José M., López, Óscar, Fernández-Bolaños, José G., "Straightforward access to novel mitochondriotropics derived from 2-arylethanol as potent and selective antiproliferative agents" in European Journal of Medicinal Chemistry, 228 (2022):113980,
https://doi.org/10.1016/j.ejmech.2021.113980 . .

TY  - DATA
AU  - Hicke, Francisco J.
AU  - Puerta, Adrián
AU  - Dinić, Jelena
AU  - Pešić, Milica
AU  - Padrón, José M.
AU  - López, Óscar
AU  - Fernández-Bolaños, José G.
PY  - 2022
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/4870
PB  - Elsevier
T2  - European Journal of Medicinal Chemistry
T1  - Supplementary data for article: Hicke, F. J.; Puerta, A.; Dinić, J.; Pešić, M.; Padrón, J. M.; López, Ó.; Fernández-Bolaños, J. G. Straightforward Access to Novel Mitochondriotropics Derived from 2-Arylethanol as Potent and Selective Antiproliferative Agents. European Journal of Medicinal Chemistry 2022, 228, 113980. https://doi.org/10.1016/j.ejmech.2021.113980.
UR  - https://hdl.handle.net/21.15107/rcub_cherry_4870
ER  - 

@misc{
author = "Hicke, Francisco J. and Puerta, Adrián and Dinić, Jelena and Pešić, Milica and Padrón, José M. and López, Óscar and Fernández-Bolaños, José G.",
year = "2022",
publisher = "Elsevier",
journal = "European Journal of Medicinal Chemistry",
title = "Supplementary data for article: Hicke, F. J.; Puerta, A.; Dinić, J.; Pešić, M.; Padrón, J. M.; López, Ó.; Fernández-Bolaños, J. G. Straightforward Access to Novel Mitochondriotropics Derived from 2-Arylethanol as Potent and Selective Antiproliferative Agents. European Journal of Medicinal Chemistry 2022, 228, 113980. https://doi.org/10.1016/j.ejmech.2021.113980.",
url = "https://hdl.handle.net/21.15107/rcub_cherry_4870"
}

Hicke, F. J., Puerta, A., Dinić, J., Pešić, M., Padrón, J. M., López, Ó.,& Fernández-Bolaños, J. G.. (2022). Supplementary data for article: Hicke, F. J.; Puerta, A.; Dinić, J.; Pešić, M.; Padrón, J. M.; López, Ó.; Fernández-Bolaños, J. G. Straightforward Access to Novel Mitochondriotropics Derived from 2-Arylethanol as Potent and Selective Antiproliferative Agents. European Journal of Medicinal Chemistry 2022, 228, 113980. https://doi.org/10.1016/j.ejmech.2021.113980.. in European Journal of Medicinal Chemistry
Elsevier..
https://hdl.handle.net/21.15107/rcub_cherry_4870

Hicke FJ, Puerta A, Dinić J, Pešić M, Padrón JM, López Ó, Fernández-Bolaños JG. Supplementary data for article: Hicke, F. J.; Puerta, A.; Dinić, J.; Pešić, M.; Padrón, J. M.; López, Ó.; Fernández-Bolaños, J. G. Straightforward Access to Novel Mitochondriotropics Derived from 2-Arylethanol as Potent and Selective Antiproliferative Agents. European Journal of Medicinal Chemistry 2022, 228, 113980. https://doi.org/10.1016/j.ejmech.2021.113980.. in European Journal of Medicinal Chemistry. 2022;.
https://hdl.handle.net/21.15107/rcub_cherry_4870 .

Hicke, Francisco J., Puerta, Adrián, Dinić, Jelena, Pešić, Milica, Padrón, José M., López, Óscar, Fernández-Bolaños, José G., "Supplementary data for article: Hicke, F. J.; Puerta, A.; Dinić, J.; Pešić, M.; Padrón, J. M.; López, Ó.; Fernández-Bolaños, J. G. Straightforward Access to Novel Mitochondriotropics Derived from 2-Arylethanol as Potent and Selective Antiproliferative Agents. European Journal of Medicinal Chemistry 2022, 228, 113980. https://doi.org/10.1016/j.ejmech.2021.113980." in European Journal of Medicinal Chemistry (2022),
https://hdl.handle.net/21.15107/rcub_cherry_4870 .

TY  - JOUR
AU  - Dinić, Jelena
AU  - Podolski-Renić, Ana
AU  - Jeremić, Marko
AU  - Pešić, Milica
PY  - 2018
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3750
AB  - Medicinal value of natural products comes from symbiotic and competitive evolution in Earth’s complex biosphere. Billions of years of co-evolutionary interactions among millions of species have produced a large repertoire of defense molecules effective in fighting bacteria, viral, and fungal pathogens. Each species contains millions of different and useful molecules and new research technologies enabled the screening of molecules and complex mixtures from diverse biological sources. Traditional use of plants and other species led to the discovery of many bioactive compounds with various properties. In the last four decades, a large number of them were evaluated for their potential to treat cancer. Penetration of drugs into the cancer cell is necessary for their lethal pharmacological effect through interaction with intracellular target molecules. Increased activity of membrane efflux pumps reduces the intracellular drug accumulation, thereby preventing drug-target interactions. The discovery of the efflux transporter P-glycoprotein (P-gp) in multidrug resistant (MDR) cancer cells prompted the efforts in overcoming drug resistance by P-gp inhibition. The search for nontoxic anticancer agents from natural sources able to overcome MDR has been imperative in the field of drug design and discovery. Herein, we review various natural compounds from diverse sources emphasizing their potential to inhibit P-gp activity and/or expression.
PB  - Bentham Science Publishers B.V.
T2  - Current Pharmaceutical Design
T1  - Potential of natural-based anticancer compounds for P-glycoprotein inhibition
VL  - 24
IS  - 36
SP  - 4334
EP  - 4354
DO  - 10.2174/1381612825666190112164211
ER  - 

@article{
author = "Dinić, Jelena and Podolski-Renić, Ana and Jeremić, Marko and Pešić, Milica",
year = "2018",
abstract = "Medicinal value of natural products comes from symbiotic and competitive evolution in Earth’s complex biosphere. Billions of years of co-evolutionary interactions among millions of species have produced a large repertoire of defense molecules effective in fighting bacteria, viral, and fungal pathogens. Each species contains millions of different and useful molecules and new research technologies enabled the screening of molecules and complex mixtures from diverse biological sources. Traditional use of plants and other species led to the discovery of many bioactive compounds with various properties. In the last four decades, a large number of them were evaluated for their potential to treat cancer. Penetration of drugs into the cancer cell is necessary for their lethal pharmacological effect through interaction with intracellular target molecules. Increased activity of membrane efflux pumps reduces the intracellular drug accumulation, thereby preventing drug-target interactions. The discovery of the efflux transporter P-glycoprotein (P-gp) in multidrug resistant (MDR) cancer cells prompted the efforts in overcoming drug resistance by P-gp inhibition. The search for nontoxic anticancer agents from natural sources able to overcome MDR has been imperative in the field of drug design and discovery. Herein, we review various natural compounds from diverse sources emphasizing their potential to inhibit P-gp activity and/or expression.",
publisher = "Bentham Science Publishers B.V.",
journal = "Current Pharmaceutical Design",
title = "Potential of natural-based anticancer compounds for P-glycoprotein inhibition",
volume = "24",
number = "36",
pages = "4334-4354",
doi = "10.2174/1381612825666190112164211"
}

Dinić, J., Podolski-Renić, A., Jeremić, M.,& Pešić, M.. (2018). Potential of natural-based anticancer compounds for P-glycoprotein inhibition. in Current Pharmaceutical Design
Bentham Science Publishers B.V.., 24(36), 4334-4354.
https://doi.org/10.2174/1381612825666190112164211

Dinić J, Podolski-Renić A, Jeremić M, Pešić M. Potential of natural-based anticancer compounds for P-glycoprotein inhibition. in Current Pharmaceutical Design. 2018;24(36):4334-4354.
doi:10.2174/1381612825666190112164211 .

Dinić, Jelena, Podolski-Renić, Ana, Jeremić, Marko, Pešić, Milica, "Potential of natural-based anticancer compounds for P-glycoprotein inhibition" in Current Pharmaceutical Design, 24, no. 36 (2018):4334-4354,
https://doi.org/10.2174/1381612825666190112164211 . .

TY  - DATA
AU  - Jeremić, Marko
AU  - Pešić, Milica
AU  - Dinić, Jelena
AU  - Banković, Jasna
AU  - Novaković, Irena T.
AU  - Šegan, Dejan M.
AU  - Sladić, Dušan
PY  - 2016
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3612
PB  - Elsevier France-Editions Scientifiques Medicales Elsevier, Paris
T2  - European Journal of Medicinal Chemistry
T1  - Supplementary material for the article: Jeremić, M.; Pešić, M.; Dinić, J.; Banković, J.; Novakovićc, I.; Šegan, D.; Sladić, D. Simple Avarone Mimetics as Selective Agents against Multidrug Resistant Cancer Cells. European Journal of Medicinal Chemistry 2016, 118, 107–120. https://doi.org/10.1016/j.ejmech.2016.04.011
UR  - https://hdl.handle.net/21.15107/rcub_cherry_3612
ER  - 

@misc{
author = "Jeremić, Marko and Pešić, Milica and Dinić, Jelena and Banković, Jasna and Novaković, Irena T. and Šegan, Dejan M. and Sladić, Dušan",
year = "2016",
publisher = "Elsevier France-Editions Scientifiques Medicales Elsevier, Paris",
journal = "European Journal of Medicinal Chemistry",
title = "Supplementary material for the article: Jeremić, M.; Pešić, M.; Dinić, J.; Banković, J.; Novakovićc, I.; Šegan, D.; Sladić, D. Simple Avarone Mimetics as Selective Agents against Multidrug Resistant Cancer Cells. European Journal of Medicinal Chemistry 2016, 118, 107–120. https://doi.org/10.1016/j.ejmech.2016.04.011",
url = "https://hdl.handle.net/21.15107/rcub_cherry_3612"
}

Jeremić, M., Pešić, M., Dinić, J., Banković, J., Novaković, I. T., Šegan, D. M.,& Sladić, D.. (2016). Supplementary material for the article: Jeremić, M.; Pešić, M.; Dinić, J.; Banković, J.; Novakovićc, I.; Šegan, D.; Sladić, D. Simple Avarone Mimetics as Selective Agents against Multidrug Resistant Cancer Cells. European Journal of Medicinal Chemistry 2016, 118, 107–120. https://doi.org/10.1016/j.ejmech.2016.04.011. in European Journal of Medicinal Chemistry
Elsevier France-Editions Scientifiques Medicales Elsevier, Paris..
https://hdl.handle.net/21.15107/rcub_cherry_3612

Jeremić M, Pešić M, Dinić J, Banković J, Novaković IT, Šegan DM, Sladić D. Supplementary material for the article: Jeremić, M.; Pešić, M.; Dinić, J.; Banković, J.; Novakovićc, I.; Šegan, D.; Sladić, D. Simple Avarone Mimetics as Selective Agents against Multidrug Resistant Cancer Cells. European Journal of Medicinal Chemistry 2016, 118, 107–120. https://doi.org/10.1016/j.ejmech.2016.04.011. in European Journal of Medicinal Chemistry. 2016;.
https://hdl.handle.net/21.15107/rcub_cherry_3612 .

Jeremić, Marko, Pešić, Milica, Dinić, Jelena, Banković, Jasna, Novaković, Irena T., Šegan, Dejan M., Sladić, Dušan, "Supplementary material for the article: Jeremić, M.; Pešić, M.; Dinić, J.; Banković, J.; Novakovićc, I.; Šegan, D.; Sladić, D. Simple Avarone Mimetics as Selective Agents against Multidrug Resistant Cancer Cells. European Journal of Medicinal Chemistry 2016, 118, 107–120. https://doi.org/10.1016/j.ejmech.2016.04.011" in European Journal of Medicinal Chemistry (2016),
https://hdl.handle.net/21.15107/rcub_cherry_3612 .

TY  - DATA
AU  - Dinić, Jelena
AU  - Novaković, Miroslav M.
AU  - Podolski-Renić, Ana
AU  - Vajs, Vlatka
AU  - Tešević, Vele
AU  - Isaković, Aleksandra J.
AU  - Pešić, Milica
PY  - 2016
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3616
PB  - Elsevier Ireland Ltd, Clare
T2  - Chemico-biological Interactions
T1  - Supplementary material for the article: Dinić, J.; Novaković, M.; Podolski-Renić, 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. Chemico-Biological Interactions 2016, 249, 36–45. https://doi.org/10.1016/j.cbi.2016.02.019
UR  - https://hdl.handle.net/21.15107/rcub_cherry_3616
ER  - 

@misc{
author = "Dinić, Jelena and Novaković, Miroslav M. and Podolski-Renić, Ana and Vajs, Vlatka and Tešević, Vele and Isaković, Aleksandra J. and Pešić, Milica",
year = "2016",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Chemico-biological Interactions",
title = "Supplementary material for the article: Dinić, J.; Novaković, M.; Podolski-Renić, 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. Chemico-Biological Interactions 2016, 249, 36–45. https://doi.org/10.1016/j.cbi.2016.02.019",
url = "https://hdl.handle.net/21.15107/rcub_cherry_3616"
}

Dinić, J., Novaković, M. M., Podolski-Renić, A., Vajs, V., Tešević, V., Isaković, A. J.,& Pešić, M.. (2016). Supplementary material for the article: Dinić, J.; Novaković, M.; Podolski-Renić, 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. Chemico-Biological Interactions 2016, 249, 36–45. https://doi.org/10.1016/j.cbi.2016.02.019. in Chemico-biological Interactions
Elsevier Ireland Ltd, Clare..
https://hdl.handle.net/21.15107/rcub_cherry_3616

Dinić J, Novaković MM, Podolski-Renić A, Vajs V, Tešević V, Isaković AJ, Pešić M. Supplementary material for the article: Dinić, J.; Novaković, M.; Podolski-Renić, 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. Chemico-Biological Interactions 2016, 249, 36–45. https://doi.org/10.1016/j.cbi.2016.02.019. in Chemico-biological Interactions. 2016;.
https://hdl.handle.net/21.15107/rcub_cherry_3616 .

Dinić, Jelena, Novaković, Miroslav M., Podolski-Renić, Ana, Vajs, Vlatka, Tešević, Vele, Isaković, Aleksandra J., Pešić, Milica, "Supplementary material for the article: Dinić, J.; Novaković, M.; Podolski-Renić, 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. Chemico-Biological Interactions 2016, 249, 36–45. https://doi.org/10.1016/j.cbi.2016.02.019" in Chemico-biological Interactions (2016),
https://hdl.handle.net/21.15107/rcub_cherry_3616 .

TY  - JOUR
AU  - Jeremić, Marko
AU  - Pešić, Milica
AU  - Dinić, Jelena
AU  - Banković, Jasna
AU  - Novaković, Irena T.
AU  - Šegan, Dejan M.
AU  - Sladić, Dušan
PY  - 2016
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2256
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. (C) 2016 Elsevier Masson SAS. All rights reserved.
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 Banković, Jasna and Novaković, Irena T. and Šegan, Dejan M. 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. (C) 2016 Elsevier Masson SAS. All rights reserved.",
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., Banković, J., Novaković, I. T., Šegan, D. M.,& 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, Banković J, Novaković IT, Šegan DM, 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, Banković, Jasna, Novaković, Irena T., Šegan, Dejan M., 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  - Novaković, Miroslav M.
AU  - Podolski-Renić, Ana
AU  - Vajs, Vlatka
AU  - Tešević, Vele
AU  - Isaković, Aleksandra J.
AU  - Pešić, Milica
PY  - 2016
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2066
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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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 M. and Podolski-Renić, Ana and Vajs, Vlatka and Tešević, Vele and Isaković, Aleksandra J. 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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.",
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. M., Podolski-Renić, A., Vajs, V., Tešević, V., Isaković, A. J.,& 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 MM, Podolski-Renić A, Vajs V, Tešević V, Isaković AJ, 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 M., Podolski-Renić, Ana, Vajs, Vlatka, Tešević, Vele, Isaković, Aleksandra J., 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  - DATA
AU  - Novaković, Miroslav M.
AU  - Pešić, Milica
AU  - Trifunović, Snežana S.
AU  - Vučković, Ivan M.
AU  - Todorović, Nina
AU  - Podolski-Renić, Ana
AU  - Dinić, Jelena
AU  - Stojković, Sonja
AU  - Tešević, Vele
AU  - Vajs, Vlatka
AU  - Milosavljević, Slobodan M.
PY  - 2014
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3662
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Phytochemistry
T1  - Supplementary data for the article: Novaković, M.; Pešić, M.; Trifunović, S.; Vučković, I.; Todorović, N.; Podolski-Renić, A.; Dinić, J.; Stojković, S.; Tešević, V.; Vajs, V.; et al. Diarylheptanoids from the Bark of Black Alder Inhibit the Growth of Sensitive and Multi-Drug Resistant Non-Small Cell Lung Carcinoma Cells. Phytochemistry 2014, 97, 46–54. https://doi.org/10.1016/j.phytochem.2013.11.001
UR  - https://hdl.handle.net/21.15107/rcub_cherry_3662
ER  - 

@misc{
author = "Novaković, Miroslav M. and Pešić, Milica and Trifunović, Snežana S. and Vučković, Ivan M. and Todorović, Nina and Podolski-Renić, Ana and Dinić, Jelena and Stojković, Sonja and Tešević, Vele and Vajs, Vlatka and Milosavljević, Slobodan M.",
year = "2014",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Phytochemistry",
title = "Supplementary data for the article: Novaković, M.; Pešić, M.; Trifunović, S.; Vučković, I.; Todorović, N.; Podolski-Renić, A.; Dinić, J.; Stojković, S.; Tešević, V.; Vajs, V.; et al. Diarylheptanoids from the Bark of Black Alder Inhibit the Growth of Sensitive and Multi-Drug Resistant Non-Small Cell Lung Carcinoma Cells. Phytochemistry 2014, 97, 46–54. https://doi.org/10.1016/j.phytochem.2013.11.001",
url = "https://hdl.handle.net/21.15107/rcub_cherry_3662"
}

Novaković, M. M., Pešić, M., Trifunović, S. S., Vučković, I. M., Todorović, N., Podolski-Renić, A., Dinić, J., Stojković, S., Tešević, V., Vajs, V.,& Milosavljević, S. M.. (2014). Supplementary data for the article: Novaković, M.; Pešić, M.; Trifunović, S.; Vučković, I.; Todorović, N.; Podolski-Renić, A.; Dinić, J.; Stojković, S.; Tešević, V.; Vajs, V.; et al. Diarylheptanoids from the Bark of Black Alder Inhibit the Growth of Sensitive and Multi-Drug Resistant Non-Small Cell Lung Carcinoma Cells. Phytochemistry 2014, 97, 46–54. https://doi.org/10.1016/j.phytochem.2013.11.001. in Phytochemistry
Pergamon-Elsevier Science Ltd, Oxford..
https://hdl.handle.net/21.15107/rcub_cherry_3662

Novaković MM, Pešić M, Trifunović SS, Vučković IM, Todorović N, Podolski-Renić A, Dinić J, Stojković S, Tešević V, Vajs V, Milosavljević SM. Supplementary data for the article: Novaković, M.; Pešić, M.; Trifunović, S.; Vučković, I.; Todorović, N.; Podolski-Renić, A.; Dinić, J.; Stojković, S.; Tešević, V.; Vajs, V.; et al. Diarylheptanoids from the Bark of Black Alder Inhibit the Growth of Sensitive and Multi-Drug Resistant Non-Small Cell Lung Carcinoma Cells. Phytochemistry 2014, 97, 46–54. https://doi.org/10.1016/j.phytochem.2013.11.001. in Phytochemistry. 2014;.
https://hdl.handle.net/21.15107/rcub_cherry_3662 .

Novaković, Miroslav M., Pešić, Milica, Trifunović, Snežana S., Vučković, Ivan M., Todorović, Nina, Podolski-Renić, Ana, Dinić, Jelena, Stojković, Sonja, Tešević, Vele, Vajs, Vlatka, Milosavljević, Slobodan M., "Supplementary data for the article: Novaković, M.; Pešić, M.; Trifunović, S.; Vučković, I.; Todorović, N.; Podolski-Renić, A.; Dinić, J.; Stojković, S.; Tešević, V.; Vajs, V.; et al. Diarylheptanoids from the Bark of Black Alder Inhibit the Growth of Sensitive and Multi-Drug Resistant Non-Small Cell Lung Carcinoma Cells. Phytochemistry 2014, 97, 46–54. https://doi.org/10.1016/j.phytochem.2013.11.001" in Phytochemistry (2014),
https://hdl.handle.net/21.15107/rcub_cherry_3662 .

TY  - JOUR
AU  - Novaković, Miroslav M.
AU  - Pešić, Milica
AU  - Trifunović, Snežana S.
AU  - Vučković, Ivan M.
AU  - Todorović, Nina
AU  - Podolski-Renić, Ana
AU  - Dinić, Jelena
AU  - Stojković, Sonja
AU  - Tešević, Vele
AU  - Vajs, Vlatka
AU  - Milosavljević, Slobodan M.
PY  - 2014
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1492
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. (C) 2013 Elsevier Ltd. All rights reserved.
PB  - Pergamon-Elsevier Science Ltd, Oxford
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 M. and Pešić, Milica and Trifunović, Snežana S. and Vučković, Ivan M. and Todorović, Nina and Podolski-Renić, Ana and Dinić, Jelena and Stojković, Sonja and Tešević, Vele and Vajs, Vlatka and Milosavljević, Slobodan M.",
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. (C) 2013 Elsevier Ltd. All rights reserved.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
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. M., Pešić, M., Trifunović, S. S., Vučković, I. M., Todorović, N., Podolski-Renić, A., Dinić, J., Stojković, S., Tešević, V., Vajs, V.,& Milosavljević, S. M.. (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
Pergamon-Elsevier Science Ltd, Oxford., 97, 46-54.
https://doi.org/10.1016/j.phytochem.2013.11.001

Novaković MM, Pešić M, Trifunović SS, Vučković IM, Todorović N, Podolski-Renić A, Dinić J, Stojković S, Tešević V, Vajs V, Milosavljević SM. 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 M., Pešić, Milica, Trifunović, Snežana S., Vučković, Ivan M., Todorović, Nina, Podolski-Renić, Ana, Dinić, Jelena, Stojković, Sonja, Tešević, Vele, Vajs, Vlatka, Milosavljević, Slobodan M., "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  - DATA
AU  - Dinić, Jelena
AU  - Novaković, Miroslav M.
AU  - Podolski-Renić, Ana
AU  - Stojković, Sonja
AU  - Mandić, Boris
AU  - Tešević, Vele
AU  - Vajs, Vlatka
AU  - Isaković, Aleksandra J.
AU  - Pešić, Milica
PY  - 2014
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3677
PB  - Georg Thieme Verlag Kg, Stuttgart
T2  - Planta Medica
T1  - Supplementary data for the article: Dinić, J.; Novaković, M.; Podolski-Renić, A.; Stojković, 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. Planta Medica 2014, 80 (13), 1088–1096. https://doi.org/10.1055/s-0034-1382993
UR  - https://hdl.handle.net/21.15107/rcub_cherry_3677
ER  - 

@misc{
author = "Dinić, Jelena and Novaković, Miroslav M. and Podolski-Renić, Ana and Stojković, Sonja and Mandić, Boris and Tešević, Vele and Vajs, Vlatka and Isaković, Aleksandra J. and Pešić, Milica",
year = "2014",
publisher = "Georg Thieme Verlag Kg, Stuttgart",
journal = "Planta Medica",
title = "Supplementary data for the article: Dinić, J.; Novaković, M.; Podolski-Renić, A.; Stojković, 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. Planta Medica 2014, 80 (13), 1088–1096. https://doi.org/10.1055/s-0034-1382993",
url = "https://hdl.handle.net/21.15107/rcub_cherry_3677"
}

Dinić, J., Novaković, M. M., Podolski-Renić, A., Stojković, S., Mandić, B., Tešević, V., Vajs, V., Isaković, A. J.,& Pešić, M.. (2014). Supplementary data for the article: Dinić, J.; Novaković, M.; Podolski-Renić, A.; Stojković, 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. Planta Medica 2014, 80 (13), 1088–1096. https://doi.org/10.1055/s-0034-1382993. in Planta Medica
Georg Thieme Verlag Kg, Stuttgart..
https://hdl.handle.net/21.15107/rcub_cherry_3677

Dinić J, Novaković MM, Podolski-Renić A, Stojković S, Mandić B, Tešević V, Vajs V, Isaković AJ, Pešić M. Supplementary data for the article: Dinić, J.; Novaković, M.; Podolski-Renić, A.; Stojković, 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. Planta Medica 2014, 80 (13), 1088–1096. https://doi.org/10.1055/s-0034-1382993. in Planta Medica. 2014;.
https://hdl.handle.net/21.15107/rcub_cherry_3677 .

Dinić, Jelena, Novaković, Miroslav M., Podolski-Renić, Ana, Stojković, Sonja, Mandić, Boris, Tešević, Vele, Vajs, Vlatka, Isaković, Aleksandra J., Pešić, Milica, "Supplementary data for the article: Dinić, J.; Novaković, M.; Podolski-Renić, A.; Stojković, 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. Planta Medica 2014, 80 (13), 1088–1096. https://doi.org/10.1055/s-0034-1382993" in Planta Medica (2014),
https://hdl.handle.net/21.15107/rcub_cherry_3677 .

TY  - JOUR
AU  - Dinić, Jelena
AU  - Novaković, Miroslav M.
AU  - Podolski-Renić, Ana
AU  - Stojković, Sonja
AU  - Mandić, Boris
AU  - Tešević, Vele
AU  - Vajs, Vlatka
AU  - Isaković, Aleksandra J.
AU  - Pešić, Milica
PY  - 2014
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1845
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 M. and Podolski-Renić, Ana and Stojković, Sonja and Mandić, Boris and Tešević, Vele and Vajs, Vlatka and Isaković, Aleksandra J. 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. M., Podolski-Renić, A., Stojković, S., Mandić, B., Tešević, V., Vajs, V., Isaković, A. J.,& 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 MM, Podolski-Renić A, Stojković S, Mandić B, Tešević V, Vajs V, Isaković AJ, 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 M., Podolski-Renić, Ana, Stojković, Sonja, Mandić, Boris, Tešević, Vele, Vajs, Vlatka, Isaković, Aleksandra J., 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 . .