TY  - JOUR
AU  - Koračak, Ljiljana
AU  - Lupšić, Ema
AU  - Terzić-Jovanović, Nataša
AU  - Jovanović, Mirna
AU  - Novaković, Miroslav
AU  - Nedialkov, Paraskev
AU  - Trendafilova, Antoaneta
AU  - Zlatović, Mario
AU  - Pešić, Milica
AU  - Opsenica, Igor
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/7172
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 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., 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 M, 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, 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 . .

TY  - JOUR
AU  - Novaković, Miroslav
AU  - Simić, Stefan
AU  - Koračak, Ljiljana
AU  - Zlatović, Mario
AU  - Ilić-Tomić, Tatjana
AU  - Asakawa, Yoshinori
AU  - Nikodinović-Runić, Jasmina
AU  - Opsenica, Igor
PY  - 2020
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/3867
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3441
AB  - Chemical and biocatalytic synthesis of seven previously undescribed marchantin A ester derivatives has been presented. Chemical synthesis afforded three peresterified bisbibenzyl products (TE1-TE3), while enzymatic method, using lipase, produced regioselective monoester derivatives (ME1-ME4). The antiproliferative activities of all prepared derivatives of marchantin A were tested on MRC-5 healthy human lung fibroblast, A549 human lung cancer, and MDA-MB-231 human breast cancer cell lines. All tested esters were less cytotoxic in comparison to marchantin A, but they also exhibited lower cytotoxicity against healthy cells. Monoesters displayed higher cytotoxic activities than the corresponding peresterified products, presumably due to the presence of free catechol group. Monohexanoyl ester ME3 displayed the same IC50 like marchantin A against MDA-MB-231 cells, but the selectivity was higher. In this way, regioselective enzymatic monoesterification enhanced selectivity of marchantin A. ME3 was also the most active among all derivatives against lung cancer cells A549 with the slightly lower activity and selectivity in comparison to marchantin A.
PB  - Elsevier
T2  - Fitoterapia
T1  - Chemo- and biocatalytic esterification of marchantin A and cytotoxic activity of ester derivatives
VL  - 142
SP  - 104520
DO  - 10.1016/j.fitote.2020.104520
ER  - 

@article{
author = "Novaković, Miroslav and Simić, Stefan and Koračak, Ljiljana and Zlatović, Mario and Ilić-Tomić, Tatjana and Asakawa, Yoshinori and Nikodinović-Runić, Jasmina and Opsenica, Igor",
year = "2020",
abstract = "Chemical and biocatalytic synthesis of seven previously undescribed marchantin A ester derivatives has been presented. Chemical synthesis afforded three peresterified bisbibenzyl products (TE1-TE3), while enzymatic method, using lipase, produced regioselective monoester derivatives (ME1-ME4). The antiproliferative activities of all prepared derivatives of marchantin A were tested on MRC-5 healthy human lung fibroblast, A549 human lung cancer, and MDA-MB-231 human breast cancer cell lines. All tested esters were less cytotoxic in comparison to marchantin A, but they also exhibited lower cytotoxicity against healthy cells. Monoesters displayed higher cytotoxic activities than the corresponding peresterified products, presumably due to the presence of free catechol group. Monohexanoyl ester ME3 displayed the same IC50 like marchantin A against MDA-MB-231 cells, but the selectivity was higher. In this way, regioselective enzymatic monoesterification enhanced selectivity of marchantin A. ME3 was also the most active among all derivatives against lung cancer cells A549 with the slightly lower activity and selectivity in comparison to marchantin A.",
publisher = "Elsevier",
journal = "Fitoterapia",
title = "Chemo- and biocatalytic esterification of marchantin A and cytotoxic activity of ester derivatives",
volume = "142",
pages = "104520",
doi = "10.1016/j.fitote.2020.104520"
}

Novaković, M., Simić, S., Koračak, L., Zlatović, M., Ilić-Tomić, T., Asakawa, Y., Nikodinović-Runić, J.,& Opsenica, I.. (2020). Chemo- and biocatalytic esterification of marchantin A and cytotoxic activity of ester derivatives. in Fitoterapia
Elsevier., 142, 104520.
https://doi.org/10.1016/j.fitote.2020.104520

Novaković M, Simić S, Koračak L, Zlatović M, Ilić-Tomić T, Asakawa Y, Nikodinović-Runić J, Opsenica I. Chemo- and biocatalytic esterification of marchantin A and cytotoxic activity of ester derivatives. in Fitoterapia. 2020;142:104520.
doi:10.1016/j.fitote.2020.104520 .

Novaković, Miroslav, Simić, Stefan, Koračak, Ljiljana, Zlatović, Mario, Ilić-Tomić, Tatjana, Asakawa, Yoshinori, Nikodinović-Runić, Jasmina, Opsenica, Igor, "Chemo- and biocatalytic esterification of marchantin A and cytotoxic activity of ester derivatives" in Fitoterapia, 142 (2020):104520,
https://doi.org/10.1016/j.fitote.2020.104520 . .

TY  - JOUR
AU  - Novaković, Miroslav
AU  - Simić, Stefan
AU  - Koračak, Ljiljana
AU  - Zlatović, Mario
AU  - Ilić-Tomić, Tatjana
AU  - Asakawa, Yoshinori
AU  - Nikodinović-Runić, Jasmina
AU  - Opsenica, Igor
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3449
AB  - Chemical and biocatalytic synthesis of seven previously undescribed marchantin A ester derivatives has been presented. Chemical synthesis afforded three peresterified bisbibenzyl products (TE1-TE3), while enzymatic method, using lipase, produced regioselective monoester derivatives (ME1-ME4). The antiproliferative activities of all prepared derivatives of marchantin A were tested on MRC-5 healthy human lung fibroblast, A549 human lung cancer, and MDA-MB-231 human breast cancer cell lines. All tested esters were less cytotoxic in comparison to marchantin A, but they also exhibited lower cytotoxicity against healthy cells. Monoesters displayed higher cytotoxic activities than the corresponding peresterified products, presumably due to the presence of free catechol group. Monohexanoyl ester ME3 displayed the same IC50 like marchantin A against MDA-MB-231 cells, but the selectivity was higher. In this way, regioselective enzymatic monoesterification enhanced selectivity of marchantin A. ME3 was also the most active among all derivatives against lung cancer cells A549 with the slightly lower activity and selectivity in comparison to marchantin A.
PB  - Elsevier
T2  - Fitoterapia
T1  - Chemo- and biocatalytic esterification of marchantin A and cytotoxic activity of ester derivatives
VL  - 142
SP  - 104520
DO  - 10.1016/j.fitote.2020.104520
ER  - 

@article{
author = "Novaković, Miroslav and Simić, Stefan and Koračak, Ljiljana and Zlatović, Mario and Ilić-Tomić, Tatjana and Asakawa, Yoshinori and Nikodinović-Runić, Jasmina and Opsenica, Igor",
year = "2020",
abstract = "Chemical and biocatalytic synthesis of seven previously undescribed marchantin A ester derivatives has been presented. Chemical synthesis afforded three peresterified bisbibenzyl products (TE1-TE3), while enzymatic method, using lipase, produced regioselective monoester derivatives (ME1-ME4). The antiproliferative activities of all prepared derivatives of marchantin A were tested on MRC-5 healthy human lung fibroblast, A549 human lung cancer, and MDA-MB-231 human breast cancer cell lines. All tested esters were less cytotoxic in comparison to marchantin A, but they also exhibited lower cytotoxicity against healthy cells. Monoesters displayed higher cytotoxic activities than the corresponding peresterified products, presumably due to the presence of free catechol group. Monohexanoyl ester ME3 displayed the same IC50 like marchantin A against MDA-MB-231 cells, but the selectivity was higher. In this way, regioselective enzymatic monoesterification enhanced selectivity of marchantin A. ME3 was also the most active among all derivatives against lung cancer cells A549 with the slightly lower activity and selectivity in comparison to marchantin A.",
publisher = "Elsevier",
journal = "Fitoterapia",
title = "Chemo- and biocatalytic esterification of marchantin A and cytotoxic activity of ester derivatives",
volume = "142",
pages = "104520",
doi = "10.1016/j.fitote.2020.104520"
}

Novaković, M., Simić, S., Koračak, L., Zlatović, M., Ilić-Tomić, T., Asakawa, Y., Nikodinović-Runić, J.,& Opsenica, I.. (2020). Chemo- and biocatalytic esterification of marchantin A and cytotoxic activity of ester derivatives. in Fitoterapia
Elsevier., 142, 104520.
https://doi.org/10.1016/j.fitote.2020.104520

Novaković M, Simić S, Koračak L, Zlatović M, Ilić-Tomić T, Asakawa Y, Nikodinović-Runić J, Opsenica I. Chemo- and biocatalytic esterification of marchantin A and cytotoxic activity of ester derivatives. in Fitoterapia. 2020;142:104520.
doi:10.1016/j.fitote.2020.104520 .

Novaković, Miroslav, Simić, Stefan, Koračak, Ljiljana, Zlatović, Mario, Ilić-Tomić, Tatjana, Asakawa, Yoshinori, Nikodinović-Runić, Jasmina, Opsenica, Igor, "Chemo- and biocatalytic esterification of marchantin A and cytotoxic activity of ester derivatives" in Fitoterapia, 142 (2020):104520,
https://doi.org/10.1016/j.fitote.2020.104520 . .