含三氟甲基的马蹄金素衍生物的合成及抗HBV活性  

Synthesis and anti-HBV Activity of Dipeptide Mimetics of Matijin-Su Containing Trifluoromethyl

作　　者：况安香 黄维杰 刘斌 徐广灿 梁光义[1,2] 徐必学 孟雪玲[1,2] 曾晓萍 KUANG Anxiang;HUANG Weijie;LIU Bin;XU Guangcan;LIANG Guangyi;XU Bixue;MENG Xueling;ZENG Xiaoping(State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine,Guizhou Medical University,Guizhou Guiyang 550014;Natural Products Research Center of Guizhou Province,Guizhou Provincial Engineering Research Center for Natural Drugs,Guizhou Guiyang 550014;College of Pharmacy,Guizhou University of Traditional Chinese Medicine,Guizhou Guiyang 550025;Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D,Guizhou Guiyang 561113;School of Pharmaceutical Sciences,Guizhou Medical University,Guizhou Guiyang 561113,China)

机构地区：[1]贵州医科大学中药功效成分发掘与利用全国重点实验室,贵州贵阳550014 [2]贵州省天然产物研究中心/贵州省天然药物工程研究中心,贵州贵阳550014 [3]贵州中医药大学药学院,贵州贵阳550025 [4]贵州医科大学贵州省化学合成药物研发利用工程技术研究中心,贵州贵阳561113 [5]贵州医科大学药学院,贵州贵阳561113

出　　处：《广州化工》2025年第5期74-77,共4页GuangZhou Chemical Industry

基　　金：贵州省科技计划项目(黔科合支撑[2021]一般422);黔科合基础-ZK[2022]一般363;国家自然科学基金项目(81760623)。

摘　　要：利用生物电子等排原理,将具有抗乙肝病毒活性的马蹄金素(MTS)衍生物中酰胺(肽)键替换为三氟甲基取代甲氨单元,设计合成了系列新型MTS二肽模拟物,以克服MTS衍生物在体内代谢不稳定的问题。所有目标化合物均通过NMR、HRMS等进行了结构确证,采用MTT法测定目标化合物的IC_(50)值。体外生物活性测试结果表明,化合物11c、11k具有显著的抗乙肝病毒活性,IC_(50)值分别为0.79、0.82μmol/L且无明显的细胞毒性。该研究结果为含氟取代的马蹄金素类模拟物的结构优化奠定了基础,具有进一步研究的价值。Matijin-Su displays strong anti-HBV activity.In order to improve the metabolic stability of MTS in vivo,a series of novel dipeptide mimetics of Matijin-Su containing trifluoromethyl were designed and synthesized by the principle of bioisosterism,and their structures were identified by NMR and HRMS,etc.In vitro biological evaluation demonstrated that compounds 11c and 11k showed the strongest anti-HBV activity with IC_(50) of 0.79 and 0.82μmol/L,and no obvious cytotoxic effect on 2.2.15 cells was observed at 100μmol/L.The research results laid the foundation for the structural optimization of fluorine substituted mimetics of Matijin-Su,and deserved to further research.

关 键 词：马蹄金素 二肽模拟物 三氟甲基 抗HBV活性 

分 类 号：R914.5[医药卫生—药物化学]