Fási, Laura and Gonda, Tímea and Tóth, Noémi and Vass, Máté and Gyovai, András and Nagy, Viktória and Ocsovszki, Imre and Zupkó, István and Kúsz, Norbert and Nové, Márta and Spengler, Gabriella and Berkecz, Róbert and Wang, Hui-Chun and Chang, Fang-Rong and Hunyadi, Attila (2024) Preparation of Dearomatized P‐Coumaric Acid Derivatives as DNA Damage Response Inhibitors with Potent in vitro Antitumo Effect. CHEMMEDCHEM : AN OFFICIAL JOURNAL OF THE EFMC. pp. 1-8. ISSN 1860-7179 (print); 1860-7187 (online)
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Abstract
Our research group previously identified graviquinone (1) as a promising antitumor metabolite that is formed in situ when the antioxidant methyl caffeate scavenges free radicals. Furthermore, it exerted a DNA damaging effect on cancer cells and a DNA protective effect on normal keratinocytes. To expand and explore chemical space around qraviquinone, in the current work we synthesized 9 new alkyl‐substituted derivatives and tested their in vitro antitumor potential. All new compounds bypassed ABCB1‐mediated multidrug resistance and showed highly different cell line specificity compared with 1. All compounds were more potent in MDA‐MB‐231 than on MCF‐7 cells. The n‐butyl‐substituted derivatives 2 and 8 modulated the cell cycle and inhibited the ATR‐mediated phosphorylation of checkpoint kinase‐1 in MCF‐7 cells. As a significant expansion of our previous findings, our results highlight the potential antitumor value of alkyl‐substituted graviquinone derivatives.
Item Type: | Article |
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Uncontrolled Keywords: | hydroxycinnamic acid derivative, alkylation, triplenegative breast cancer, multidrug resistance, DNA damage, ATR |
Subjects: | R Medicine / orvostudomány > RC Internal medicine / belgyógyászat > RC0254 Neoplasms. Tumors. Oncology (including Cancer) / daganatok, tumorok, onkológia |
SWORD Depositor: | MTMT SWORD |
Depositing User: | MTMT SWORD |
Date Deposited: | 02 Jul 2024 13:06 |
Last Modified: | 02 Jul 2024 13:06 |
URI: | https://real.mtak.hu/id/eprint/199213 |
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