Discovery of the Biginelli hybrids as novel caspase-9 activators in apoptotic machines: Lipophilicity, molecular docking study, influence on angiogenesis gene and miR-21 expression levels.

摘要: Abstract In order to investigate potential therapeutically agents, novel products of Biginelli reaction (4a-l) were synthesized and exposed cytotoxic caspase activities, angiogenesis, cell cycle distribution, gene microRNA expression levels, lipophilicity assessment docking study. Among the twelve compounds evaluated for activity, five them (4c, 4d, 4f, 4k 4l) that showed excellent activity on tested lines (HeLa, LS174 A549) selected further evaluation. Interestingly, compound 4f has up three times higher selectivity index (SI) towards cancer cells than cisplatin (on HeLa, A549 SI = 18.2, 13.5 11.2, respectively). The obtained results from distribution indicate promoted caspase-9 activation, implicated in intrinsic pathway apoptosis. Lipophilicity 4a-l was determinate by using reversed-phase high-performance liquid chromatography.