苯异噁唑基莽草酰胺衍生物的合成与体外抗乙肝病毒活性研究

Synthesis and in vitro anti-HBV activity of benzoxazole based shikimamide derivatives

针对市场上的抗乙肝病毒药物存在毒副作用、耐药性等问题,为进一步研发新的抗乙肝病毒有效药物,以莽草酸为原料设计合成了22个苯异噁唑基莽草酰胺类化合物,用1H NMR、13C NMR和MS方法对化合物的结构进行表征,并对合成得到的化合物进行抗乙肝病毒体外活性实验。结果表明:苯异噁唑基莽草酰胺衍生物的毒性低,化合物11、14、15、17较好地抑制乙肝病毒HBeAg和HBsAg的分泌。活性化合物的分子对接结果显示,化合物与核心蛋白片段(PDB ID 3KXS)具有较好的相互作用。

Shikimic amides with isoxazole fragments were designed for non-nucleoside anti-HBV agents, 22 new isoxazole derivatives were designed and synthesized, and their structures were determined by ~1 HNMR,13CNMR, and MS methods.The results of bioactive assay for anti-HBV activity with HepG2.2.15 cell showed that all the target compounds were low toxicity, compounds 11、14、15 and 17 among them inhibited secretion of HBeAg and HBsAg from HBV obviously.Results of molecular docking studies showed these bioactive compounds binding to HBV core protein residue(PDB ID 3kxs) with good interactions.