4-氯苯甲酸取代马蹄金素衍生物的合成及其抗HBV活性研究  

Synthesis and anti-HBV activity of 4-chlorobenzoic acid substituted derivative of Matijin-Su

作　　者：邵晓霜 张彦功 曾晓萍[2,3] 赵能武[1] 梁光义[1,2,3] 徐必学 SHAO Xiao-shuang;ZHANG Yan-gong;ZENG Xiao-ping;ZHAO Neng-Wu;LIANG Guangyi;XU Bi-xue(Guizhou University of Traditional Chinese Medicine,Guiyang 550025;State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University,Guiyang 550014;The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences/Guizhou Provincial Engineering Research Center for Natural Drugs,Guiyang 550014)

机构地区：[1]贵州中医药大学,贵阳550025 [2]贵州医科大学省部共建药用植物功效与利用国家重点实验室,贵阳550014 [3]贵州省中国科学院天然产物化学重点实验室/贵州省天然药物工程研究中心,贵阳550014

出　　处：《中南药学》2020年第2期177-182,共6页Central South Pharmacy

基　　金：国家自然科学基金资助项目(No.81760623);贵阳中医学院研究生工作站创新项目[No.GNYL(2017)008号-7-Y];贵州省高层次创新型人才“百层次”资助项目(黔科合平台人才【2016】5678);黔科合平台人才(【2017】5737)。

摘　　要：目的设计和合成含4-氯苯甲酸取代马蹄金素(Matijin-Su,MTS)衍生物,以期寻找到抗乙肝病毒(HBV)活性更强的MTS衍生物。方法以马蹄金素为先导化合物,通过引入4-氯苯甲酸取代,设计合成一系列MTS衍生物并对其进行抗HBV活性测试。结果设计合成了4-氯苯甲酸取代的MTS衍生物11个(3、4a、4b、4c、4d、4e、4f、4g、4h、4i、5),其中化合物4b、4d、4e、4h表现出良好的抗HBV活性,IC50分别为9.19、15.30、13.48、14.90μmol·L-1。结论 4-氯苯甲酸取代的MTS衍生物具有更强的抗HBV活性,具有进一步研究的价值。Objective To design and synthesize derivatives of Matijin-Su(MTS) containing 4-chlorobenzoic acid substitution and to develop new anti-hepatitis B virus(HBV) agents with high anti-HBV activity. Methods MTS was used as a lead compound, a series of 4-chlorobenzoic acid substituted derivatives of MTS were synthesized and evaluated anti-HBV activity. Results Eleven new 4-chlorobenzoic acid substituted derivatives of MTS(3, 4 a, 4 b, 4 c, 4 d, 4 e, 4 f, 4 g, 4 h, 4 i, 5) were synthesized. Compounds 4 b, 4 d, 4 e, and 4 h exhibited effective activities against the replication of HBV DNA with IC50 values of 9.19, 15.30, 13.48, and 14.90 μmol·L-1 respectively. Conclusion Incorporation of 4-chlorobenzoic acid substitution into MTS derivatives may improve their anti-HBV activity.

关 键 词：马蹄金素 4-氯苯甲酸取代 合成 抗乙肝病毒活性 

分 类 号：R284[医药卫生—中药学] R285[医药卫生—中医学]