TY  - JOUR
AU  - Fási, Laura
AU  - Di Meo, Florent
AU  - Kuo, Ching-Ying
AU  - Stojković Burić, Sonja
AU  - Martins, Ana
AU  - Kúsz, Norbert
AU  - Béni, Zoltán
AU  - Dékány, Miklós
AU  - Balogh, György Tibor
AU  - Pešić, Milica
AU  - Wang, Hui-Chun
AU  - Trouillas, Patrick
AU  - Hunyadi, Attila
PY  - 2019
UR  - http://pubs.acs.org/doi/10.1021/acs.jmedchem.8b01994
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3278
AB  - Cancer cells generally possess higher levels of reactive oxygen species than normal cells, and this can serve as a possible therapeutic target. In this proof-of-concept study, an antioxidant-inspired drug discovery strategy was evaluated using a hydroxycinnamic acid derivative. The processing of oxidized mixtures of p-coumaric acid methyl ester (pcm) revealed a new antitumor lead, graviquinone. Graviquinone bypassed ABCB1-mediated resistance, induced DNA damage in lung carcinoma cells but exerted DNA protective activity in normal keratinocytes, and modulated DNA damage response in MCF-7 cells. The cytotoxic effect of pcm in MCF-7 cells was potentiated under H2O2-induced oxidative stress, and the formation of graviquinone was confirmed by Fenton's reaction on pcm. In silico DFT calculations suggested graviquinone as a kinetic product of pcm scavenging •OH radicals. Our results demonstrate the pharmacological value of an in situ-formed, oxidative stress-related metabolite of an antioxidant. This might be of particular importance for designing new strategies for antioxidant-based drug discovery.
T2  - Journal of Medicinal Chemistry
T1  - Antioxidant-inspired drug discovery: antitumor metabolite is formed in situ from a hydroxycinnamic acid derivative upon free radical scavenging.
IS  - 3
VL  - 62
DO  - 10.1021/acs.jmedchem.8b01994
SP  - 1657
EP  - 1668
ER  - 

@article{
author = "Fási, Laura and Di Meo, Florent and Kuo, Ching-Ying and Stojković Burić, Sonja and Martins, Ana and Kúsz, Norbert and Béni, Zoltán and Dékány, Miklós and Balogh, György Tibor and Pešić, Milica and Wang, Hui-Chun and Trouillas, Patrick and Hunyadi, Attila",
year = "2019",
abstract = "Cancer cells generally possess higher levels of reactive oxygen species than normal cells, and this can serve as a possible therapeutic target. In this proof-of-concept study, an antioxidant-inspired drug discovery strategy was evaluated using a hydroxycinnamic acid derivative. The processing of oxidized mixtures of p-coumaric acid methyl ester (pcm) revealed a new antitumor lead, graviquinone. Graviquinone bypassed ABCB1-mediated resistance, induced DNA damage in lung carcinoma cells but exerted DNA protective activity in normal keratinocytes, and modulated DNA damage response in MCF-7 cells. The cytotoxic effect of pcm in MCF-7 cells was potentiated under H2O2-induced oxidative stress, and the formation of graviquinone was confirmed by Fenton's reaction on pcm. In silico DFT calculations suggested graviquinone as a kinetic product of pcm scavenging •OH radicals. Our results demonstrate the pharmacological value of an in situ-formed, oxidative stress-related metabolite of an antioxidant. This might be of particular importance for designing new strategies for antioxidant-based drug discovery.",
journal = "Journal of Medicinal Chemistry",
title = "Antioxidant-inspired drug discovery: antitumor metabolite is formed in situ from a hydroxycinnamic acid derivative upon free radical scavenging.",
number = "3",
volume = "62",
doi = "10.1021/acs.jmedchem.8b01994",
pages = "1657-1668"
}

Fási, L., Di Meo, F., Kuo, C., Stojković Burić, S., Martins, A., Kúsz, N., Béni, Z., Dékány, M., Balogh, G. T., Pešić, M., Wang, H., Trouillas, P.,& Hunyadi, A.. (2019). Antioxidant-inspired drug discovery: antitumor metabolite is formed in situ from a hydroxycinnamic acid derivative upon free radical scavenging.. in Journal of Medicinal Chemistry, 62(3), 1657-1668.
https://doi.org/10.1021/acs.jmedchem.8b01994

Fási L, Di Meo F, Kuo C, Stojković Burić S, Martins A, Kúsz N, Béni Z, Dékány M, Balogh GT, Pešić M, Wang H, Trouillas P, Hunyadi A. Antioxidant-inspired drug discovery: antitumor metabolite is formed in situ from a hydroxycinnamic acid derivative upon free radical scavenging.. in Journal of Medicinal Chemistry. 2019;62(3):1657-1668.
doi:10.1021/acs.jmedchem.8b01994 .

Fási, Laura, Di Meo, Florent, Kuo, Ching-Ying, Stojković Burić, Sonja, Martins, Ana, Kúsz, Norbert, Béni, Zoltán, Dékány, Miklós, Balogh, György Tibor, Pešić, Milica, Wang, Hui-Chun, Trouillas, Patrick, Hunyadi, Attila, "Antioxidant-inspired drug discovery: antitumor metabolite is formed in situ from a hydroxycinnamic acid derivative upon free radical scavenging." in Journal of Medicinal Chemistry, 62, no. 3 (2019):1657-1668,
https://doi.org/10.1021/acs.jmedchem.8b01994 . .