药学学报, 2016, 51(10): 1578-1583
引用本文:
崔新华, 谭洁, 周敏, 韦万兴, 刘旭, 王立升. 肟类衍生物的设计、虚拟筛选、合成与体外抗乙肝病毒活性研究[J]. 药学学报, 2016, 51(10): 1578-1583.
CUI Xin-hua, TAN Jie, ZHOU Min, WEI Wan-xing, LIU Xu, WANG Li-sheng. Design, virtual screening, synthesis and anti-hepatitis B virus of oxime derivatives[J]. Acta Pharmaceutica Sinica, 2016, 51(10): 1578-1583.

肟类衍生物的设计、虚拟筛选、合成与体外抗乙肝病毒活性研究
崔新华, 谭洁, 周敏, 韦万兴, 刘旭, 王立升
广西大学化学化工学院, 广西 南宁 530004
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、13C 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IC50和治疗指数分别为IC50 HBsAg=81.15μmol·L-1、SIHBsAg=9.20;IC50 HBeAg=90.66 μmol·L-1、SIHBeAg8.24。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。
关键词:          肟醚      合成      分子对接      抗乙肝病毒活性     
Design, virtual screening, synthesis and anti-hepatitis B virus of oxime derivatives
CUI Xin-hua, TAN Jie, ZHOU Min, WEI Wan-xing, LIU Xu, WANG Li-sheng
School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China
Abstract:
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 μmol·L-1, SIHBsAg=9.20 and IC50 HBeAg=90.66 μmol·L-1, SIHBeAg8.24, respectively. Preliminary structure-activity relationship study shows that methyl oxime ethers displayed better anti-HBV activities than the oximes.
Key words:    oxime    oxime ether    synthesis    molecular docking    anti-HBV activity   
收稿日期: 2016-05-03
DOI: 10.16438/j.0513-4870.2016-0418
基金项目: 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及卓越学者计划(2015年起).
通讯作者: 韦万兴
Email: wxwei@gxu.edu.cn
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