摘要
本文设计了一系列新型结构的肟及肟醚化合物,通过分子对接进行虚拟筛选。以苯、甲苯、甲氧基苯、氯苯为初始原料合成12个新化合物,其中肟类4个、肟醚类8个,并对其结构进行了~1H NMR、^(13)C NMR和MS确认。体外活性测试结果表明,部分目标化合物具有一定的抗乙肝病毒活性且毒性较小。其中化合物4B-2抑制活性最好,其对表面抗原(HBsAg)与e抗原(HBeAg)的抑制活性IC_(50)和治疗指数分别为IC_(50 HBsAg)=81.15μmol·L^(-1)、SI_(HBsAg)=9.20;IC_(50 HBeAg)=90.66μmol·L^(-1)、SI_(HBeAg)=8.24。初步的构效关系显示甲基肟醚类化合物活性较好,为新抗乙肝药物的研究提供参考。
A series of new oxime and oxime ethers compounds were designed and virtually screened with target using the Molecular Operating Environment （MOE） software. Twelve unreported compounds including 4 oximes and 8 oxime ethers were synthesized with benzene, toluene, methoxybenzene and chlorobenzene as initial raw materials. Structures of compounds were elucidated by 1H NMR, 13C NMR and MS. The results of bioactive screening showed that a part of compounds displayed obviously anti-HBV activities. Inhibitory activities of compounds 4B-2 in secretion of HBsAg and HBeAg were IC50 HBsAg=81.15 μmolL-1, SIHBsAg=9.20 and IC50 HBeAg=90.66 μmolL-1, SIHBeAg8.24, respectively. Preliminary structure-activity relationship study shows that methyl oxime ethers displayed better anti-HBV activities than the oximes.
出处
《药学学报》
CAS
CSCD
北大核心
2016年第10期1578-1583,共6页
Acta Pharmaceutica Sinica
基金
国家自然科学基金资助项目(81060261)
广西自然科学基金资助项目(2012GXNSFAA053021)
广西壮族自治区教育厅广西高等学校高水平创新团队
卓越学者计划(2015年起)
关键词
肟
肟醚
合成
分子对接
抗乙肝病毒活性
oxime oxime ether synthesis molecular docking anti-HBV activity
