Synthesis, anticancer evaluation and mechanism studies of novel indolequinone derivatives of ursolic acid.

摘要: Abstract A series of novel indolequinone derivatives ursolic acid bearing ester, hydrazide, or amide moieties were designed, synthesized, and screened for their in vitro antiproliferative activities against three cancer cell lines (MCF-7, HeLa, HepG2) a normal gastric mucosal line (Ges-1). number compounds showed significant activity tested lines. Among them, compound 6t exhibited the most potent with IC50 values 1.66 ± 0.21, 3.16 ± 0.24, 10.35 ± 1.63 µM, respectively, considerably lower cytotoxicity to Ges-1 cells. Especially, could arrest cycle at S phase, suppress migration MCF-7 cells, elevate intracellular reactive oxygen species (ROS) level, decrease mitochondrial membrane potential. Western blot analysis that upregulated Bax, cleaved caspase-3/9, PARP levels downregulated Bcl-2 level All these results indicated significantly induce apoptosis Meanwhile, markedly decreased p-AKT p-mTOR expression, which revealed probably exerted its through targeting PI3K/AKT/mTOR signaling pathway. Therefore, be promising lead discovery anticancer agents.