Hybrid molecules of protoflavones and spirooxindole derivatives with selective cytotoxicity against triple-negative breast cancer cells.

ABSTRACT: The combination of compounds with complementary bioactivities into hybrid molecules is an emerging concept in drug discovery. In this study, we aimed to synthesize new hybrid compounds based on p53-MDM2/X protein-protein interaction spiropyrazoline oxindole-based inhibitors and ataxia telangiectasia and Rad3-related (ATR) protoflavone-based inhibitors through copper(i) catalysed azide-alkyne cycloaddition. Five new hybrids were prepared along with three representative reference fragments. The compounds were tested against human breast cancer cell lines MCF-7 (hormone-dependent, wild-type p53) and MDA-MB-231 (triple-negative, mutant p53). Most of the new hybrids were more cytotoxic than their reference fragments and several showed 2-4 times selective toxicity against MDA-MB-231 cells. Relev

SUBMITTER: Girst G 

PROVIDER: S-EPMC10507806 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature