TY  - JOUR
AU  - Dinić, Jelena
AU  - Podolski-Renić, Ana
AU  - Jeremić, Marko
AU  - Pešić, Milica
PY  - 2018
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4049
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  - Sharjah: Bentham Science Publishers
T2  - Current Pharmaceutical Design
T1  - Potential of Natural-Based Anticancer Compounds for P-Glycoprotein Inhibition
IS  - 36
VL  - 24
VL  - 4354
DO  - 10.2174/1381612825666190112164211
SP  - 4334
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 = "Sharjah: Bentham Science Publishers",
journal = "Current Pharmaceutical Design",
title = "Potential of Natural-Based Anticancer Compounds for P-Glycoprotein Inhibition",
number = "36",
volume = "24, 4354",
doi = "10.2174/1381612825666190112164211",
pages = "4334"
}

Dinić, J., Podolski-Renić, A., Jeremić, M.,& Pešić, M.. (2018). Potential of Natural-Based Anticancer Compounds for P-Glycoprotein Inhibition. in Current Pharmaceutical Design
Sharjah: Bentham Science Publishers., 24(36), 4334.
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.
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,
https://doi.org/10.2174/1381612825666190112164211 . .

TY  - JOUR
AU  - Podolski-Renić, Ana
AU  - Bősze, Szilvia
AU  - Dinić, Jelena
AU  - Kocsis, László
AU  - Hudecz, Ferenc
AU  - Csámpai, Antal
AU  - Pešić, Milica
PY  - 2017
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4048
AB  - Recently, we demonstrated that ferrocene-containing compounds with a cinchona moiety displayed marked anticancer activity. Here we report on the effects of the most promising isomers encompassing quinine- (compounds 4 and 5) and quinidine-epimers (compounds 6 and 7) – synthesized using improved methods providing controlled diastereoselectivity – in three different human multidrug resistant (MDR) cancer cell lines and their sensitive counterparts (non-small cell lung carcinoma NCI-H460/R/NCI-H460, colorectal carcinoma DLD1-TxR/DLD1 and glioblastoma U87-TxR/U87). We observed that the presence of the MDR phenotype did not diminish the activity of the compounds suggesting that ferrocene quinine- and quinidine-epimers are not substrates for P-glycoprotein, which has been indicated as a major mechanism of MDR in the cell lines used. Considering that metal-based anticancer agents mainly act by increasing ROS production, we investigated the potential of ferrocene–quinidine epimers to generate ROS. We found that 6 and 7 more readily increased ROS production and induced mitochondrial damage in MDR cancer cells. According to cell death analysis, 6 and 7 were more active against MDR cancer cells showing collateral sensitivity. In addition, our data suggest that these compounds could act as inhibitors of autophagy. Importantly, simultaneous treatments of 6 and 7 with paclitaxel (PTX) increased the sensitivity of MDR cancer cells to PTX. In conclusion, the ferrocene–quinidine epimers, besides being selective towards MDR cancer cells, could also possess potential to overcome PTX resistance.
PB  - The Royal Society of Chemistry
T2  - Metallomics
T1  - Ferrocene–cinchona hybrids with triazolyl-chalcone linkers act as pro-oxidants and sensitize human cancer cell lines to paclitaxel
IS  - 8
VL  - 9
DO  - 10.1039/C7MT00183E
SP  - 1132
EP  - 1141
ER  - 

@article{
author = "Podolski-Renić, Ana and Bősze, Szilvia and Dinić, Jelena and Kocsis, László and Hudecz, Ferenc and Csámpai, Antal and Pešić, Milica",
year = "2017",
abstract = "Recently, we demonstrated that ferrocene-containing compounds with a cinchona moiety displayed marked anticancer activity. Here we report on the effects of the most promising isomers encompassing quinine- (compounds 4 and 5) and quinidine-epimers (compounds 6 and 7) – synthesized using improved methods providing controlled diastereoselectivity – in three different human multidrug resistant (MDR) cancer cell lines and their sensitive counterparts (non-small cell lung carcinoma NCI-H460/R/NCI-H460, colorectal carcinoma DLD1-TxR/DLD1 and glioblastoma U87-TxR/U87). We observed that the presence of the MDR phenotype did not diminish the activity of the compounds suggesting that ferrocene quinine- and quinidine-epimers are not substrates for P-glycoprotein, which has been indicated as a major mechanism of MDR in the cell lines used. Considering that metal-based anticancer agents mainly act by increasing ROS production, we investigated the potential of ferrocene–quinidine epimers to generate ROS. We found that 6 and 7 more readily increased ROS production and induced mitochondrial damage in MDR cancer cells. According to cell death analysis, 6 and 7 were more active against MDR cancer cells showing collateral sensitivity. In addition, our data suggest that these compounds could act as inhibitors of autophagy. Importantly, simultaneous treatments of 6 and 7 with paclitaxel (PTX) increased the sensitivity of MDR cancer cells to PTX. In conclusion, the ferrocene–quinidine epimers, besides being selective towards MDR cancer cells, could also possess potential to overcome PTX resistance.",
publisher = "The Royal Society of Chemistry",
journal = "Metallomics",
title = "Ferrocene–cinchona hybrids with triazolyl-chalcone linkers act as pro-oxidants and sensitize human cancer cell lines to paclitaxel",
number = "8",
volume = "9",
doi = "10.1039/C7MT00183E",
pages = "1132-1141"
}

Podolski-Renić, A., Bősze, S., Dinić, J., Kocsis, L., Hudecz, F., Csámpai, A.,& Pešić, M.. (2017). Ferrocene–cinchona hybrids with triazolyl-chalcone linkers act as pro-oxidants and sensitize human cancer cell lines to paclitaxel. in Metallomics
The Royal Society of Chemistry., 9(8), 1132-1141.
https://doi.org/10.1039/C7MT00183E

Podolski-Renić A, Bősze S, Dinić J, Kocsis L, Hudecz F, Csámpai A, Pešić M. Ferrocene–cinchona hybrids with triazolyl-chalcone linkers act as pro-oxidants and sensitize human cancer cell lines to paclitaxel. in Metallomics. 2017;9(8):1132-1141.
doi:10.1039/C7MT00183E .

Podolski-Renić, Ana, Bősze, Szilvia, Dinić, Jelena, Kocsis, László, Hudecz, Ferenc, Csámpai, Antal, Pešić, Milica, "Ferrocene–cinchona hybrids with triazolyl-chalcone linkers act as pro-oxidants and sensitize human cancer cell lines to paclitaxel" in Metallomics, 9, no. 8 (2017):1132-1141,
https://doi.org/10.1039/C7MT00183E . .