4-furanylvinylquinoline derivative as a new scaffold for the design of oxidative stress initiator and glucose transporters inhibitor drugs

Abstract

Abstract In the present work, a detailed analysis of the effect of a substitution at the C4 position of the quinoline ring and substituents on the structure-antitumour activity relationship was conducted. After analysing a library of derivatives from the styrylquinoline and furanylvinylquinoline groups, we selected the most active (IC50 below 100 nM) derivative 13 that contained the strongly electron-withdrawing nitro group in the furan substituent. The mechanism of action of this compound has been studied on cell lines that differ in their p53 protein status. For this derivative, both cell cycle arrest and the induction of apoptosis were revealed. These studies were then confirmed by other methods at the gene and protein levels. Interestingly, we observed differences in the mechanism of action depending on the presence and mutation of the p53 protein, thus confirming its key role in the cellular processes. Incubation with derivative 13 resulted in the induction of oxidative stress and triggered a cascade of cellular defence proteins that failed in the face of such an active compound. In addition, the results showed an inhibition of the glucose transporter, which is extremely important in the context of anti-cancer activity.