{Reference Type}: Journal Article
{Title}: Preparation of dearomatized p-coumaric acid derivatives as DNA damage response inhibitors with potent in vitro antitumor effect.
{Author}: Fási L;Gonda T;Tóth N;Vass M;Gyovai A;Nagy V;Ocsovszki I;Zupkó I;Kúsz N;Nové M;Spengler G;Berkecz R;Wang HC;Chang FR;Hunyadi A;
{Journal}: ChemMedChem
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jun 26
{Factor}: 3.54
{DOI}: 10.1002/cmdc.202300675
{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.