Novel artesunate–pyrimidine-based hybrids with anticancer potential against multidrug-resistant cancer cells
Само за регистроване кориснике
2023
Аутори
Koračak, LjiljanaLupšić, Ema
Terzić-Jovanović, Nataša
Jovanović, Mirna
Novaković, Miroslav M.
Nedialkov, Paraskev
Trendafilova, Antoaneta
Zlatović, Mario
Pešić, Milica
Opsenica, Igor
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
The synthesis of 17 hybrid molecules, consisting of artesunate, a derivative of naturally occurring artemisinin, and synthetic 4-aryl-2-aminopyrimidines, is described. New compounds were designed to improve the parent compounds' cytotoxic properties, activity, and selectivity. The synthesized hybrid molecules (15a–f with ethylenediamine linker and 16a–k with piperazine linker), as well as their precursors – pyrimidine derivatives (13a–f and 14a–k), artemisinin, and artesunate, were tested on sensitive and multidrug-resistant (MDR) human non-small cell lung carcinoma (NSCLC) cells. All hybrid compounds with piperazine linker 16a–k were selective toward NSCLC cells and displayed IC50 values below 5 μM. Although they showed similar anticancer potency as artesunate, their selectivity against cancer cells was considerably improved. Importantly, 16h–k hybrid compounds were able to evade MDR phenotype, inhibit P-glycoprotein (P-gp) activity, and increase the sensitivity of MDR NSCLC cells to ...doxorubicin (DOX). The inhibition of P-gp activity induced by 16h–j was stronger than the one obtained with artesunate. Among these four hybrid compounds, 16k was the most potent anticancer agent with similar IC50 values of around 1.5 μM (for comparison – over 3.1 μM for artesunate) in sensitive and MDR NSCLC cells.
Кључне речи:
hybrid molecules / anticancer potential / artesunate / multidrug-resistant cancer cellsИзвор:
New Journal of Chemistry, 2023, 47, 14, 6844-6855Издавач:
- Royal Society of Chemistry
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200168 (Универзитет у Београду, Хемијски факултет) (RS-MESTD-inst-2020-200168)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200026 (Универзитет у Београду, Институт за хемију, технологију и металургију - ИХТМ) (RS-MESTD-inst-2020-200026)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200007 (Универзитет у Београду, Институт за биолошка истраживања 'Синиша Станковић') (RS-MESTD-inst-2020-200007)
- Serbian Academy of Sciences and Arts
- Bulgarian Academy of Sciences
Колекције
Институција/група
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Koračak, Ljiljana AU - Lupšić, Ema AU - Terzić-Jovanović, Nataša AU - Jovanović, Mirna AU - Novaković, Miroslav M. AU - Nedialkov, Paraskev AU - Trendafilova, Antoaneta AU - Zlatović, Mario AU - Pešić, Milica AU - Opsenica, Igor PY - 2023 UR - http://cherry.chem.bg.ac.rs/handle/123456789/6245 AB - The synthesis of 17 hybrid molecules, consisting of artesunate, a derivative of naturally occurring artemisinin, and synthetic 4-aryl-2-aminopyrimidines, is described. New compounds were designed to improve the parent compounds' cytotoxic properties, activity, and selectivity. The synthesized hybrid molecules (15a–f with ethylenediamine linker and 16a–k with piperazine linker), as well as their precursors – pyrimidine derivatives (13a–f and 14a–k), artemisinin, and artesunate, were tested on sensitive and multidrug-resistant (MDR) human non-small cell lung carcinoma (NSCLC) cells. All hybrid compounds with piperazine linker 16a–k were selective toward NSCLC cells and displayed IC50 values below 5 μM. Although they showed similar anticancer potency as artesunate, their selectivity against cancer cells was considerably improved. Importantly, 16h–k hybrid compounds were able to evade MDR phenotype, inhibit P-glycoprotein (P-gp) activity, and increase the sensitivity of MDR NSCLC cells to doxorubicin (DOX). The inhibition of P-gp activity induced by 16h–j was stronger than the one obtained with artesunate. Among these four hybrid compounds, 16k was the most potent anticancer agent with similar IC50 values of around 1.5 μM (for comparison – over 3.1 μM for artesunate) in sensitive and MDR NSCLC cells. PB - Royal Society of Chemistry T2 - New Journal of Chemistry T1 - Novel artesunate–pyrimidine-based hybrids with anticancer potential against multidrug-resistant cancer cells VL - 47 IS - 14 SP - 6844 EP - 6855 DO - 10.1039/D3NJ00427A ER -
@article{ author = "Koračak, Ljiljana and Lupšić, Ema and Terzić-Jovanović, Nataša and Jovanović, Mirna and Novaković, Miroslav M. and Nedialkov, Paraskev and Trendafilova, Antoaneta and Zlatović, Mario and Pešić, Milica and Opsenica, Igor", year = "2023", abstract = "The synthesis of 17 hybrid molecules, consisting of artesunate, a derivative of naturally occurring artemisinin, and synthetic 4-aryl-2-aminopyrimidines, is described. New compounds were designed to improve the parent compounds' cytotoxic properties, activity, and selectivity. The synthesized hybrid molecules (15a–f with ethylenediamine linker and 16a–k with piperazine linker), as well as their precursors – pyrimidine derivatives (13a–f and 14a–k), artemisinin, and artesunate, were tested on sensitive and multidrug-resistant (MDR) human non-small cell lung carcinoma (NSCLC) cells. All hybrid compounds with piperazine linker 16a–k were selective toward NSCLC cells and displayed IC50 values below 5 μM. Although they showed similar anticancer potency as artesunate, their selectivity against cancer cells was considerably improved. Importantly, 16h–k hybrid compounds were able to evade MDR phenotype, inhibit P-glycoprotein (P-gp) activity, and increase the sensitivity of MDR NSCLC cells to doxorubicin (DOX). The inhibition of P-gp activity induced by 16h–j was stronger than the one obtained with artesunate. Among these four hybrid compounds, 16k was the most potent anticancer agent with similar IC50 values of around 1.5 μM (for comparison – over 3.1 μM for artesunate) in sensitive and MDR NSCLC cells.", publisher = "Royal Society of Chemistry", journal = "New Journal of Chemistry", title = "Novel artesunate–pyrimidine-based hybrids with anticancer potential against multidrug-resistant cancer cells", volume = "47", number = "14", pages = "6844-6855", doi = "10.1039/D3NJ00427A" }
Koračak, L., Lupšić, E., Terzić-Jovanović, N., Jovanović, M., Novaković, M. M., Nedialkov, P., Trendafilova, A., Zlatović, M., Pešić, M.,& Opsenica, I.. (2023). Novel artesunate–pyrimidine-based hybrids with anticancer potential against multidrug-resistant cancer cells. in New Journal of Chemistry Royal Society of Chemistry., 47(14), 6844-6855. https://doi.org/10.1039/D3NJ00427A
Koračak L, Lupšić E, Terzić-Jovanović N, Jovanović M, Novaković MM, Nedialkov P, Trendafilova A, Zlatović M, Pešić M, Opsenica I. Novel artesunate–pyrimidine-based hybrids with anticancer potential against multidrug-resistant cancer cells. in New Journal of Chemistry. 2023;47(14):6844-6855. doi:10.1039/D3NJ00427A .
Koračak, Ljiljana, Lupšić, Ema, Terzić-Jovanović, Nataša, Jovanović, Mirna, Novaković, Miroslav M., Nedialkov, Paraskev, Trendafilova, Antoaneta, Zlatović, Mario, Pešić, Milica, Opsenica, Igor, "Novel artesunate–pyrimidine-based hybrids with anticancer potential against multidrug-resistant cancer cells" in New Journal of Chemistry, 47, no. 14 (2023):6844-6855, https://doi.org/10.1039/D3NJ00427A . .