Synthesis and Antitumor Activity of Heterocylic Aurone and Its Analogue Indanone Derivatives

Abstract

– Based on non-classical bioisosterism and the rule of alkene insertion, thirty-five heterocyclic aurones and its analogue indanones derivatives were designed and synthesized. They were evaluated for inhibitory activity against HELA, HT-29 and A549 and HepG2 human cancer cell lines. Among them, twenty-five compounds exhibited moderate to excellent antitumor activity. The minimum value of IC 50 was 1.649±0.083 μM (compound B1 ). The SAR showed that aurone with B ring as aromatic heterocycles such as 4-bromothiophene, quinoline, carbazole and indanone derivatives and some or indanone were more potent than others. Besides, the introduction of acetylated glycosides was beneficial to the activity. Compounds A1 , B1 , C5 , C8 , C10 , C11 , C12 and D1 were promising antitumor agents. Among them, compounds molecular docking studies were performed between B1 , C8 and potential targets Aurora B (PBD: 2BFY). On the basis, the chemical and physical properties, as well as ADMET of active compounds were predicted and analyzed. And it showed that most of compounds had good pharmacokinetic profiles and high safety profiles