水杨酰苯胺类mglu5拮抗剂作用模式及体外抗肿瘤活性研究  

Molecular Docking of Salicylanilides with mglu5 and Their Antitumor Activity in Vitro

作　　者：张弦 周鑫[1] 尹华[1] 张昊霖 文菲 熊广华 曹德良 廖端芳[1] 傅榕赓[1] ZHANG Xian;ZHOU Xin;YIN Hua;ZHANG Haolin;WEN Fei;XIONG Guanghua;CAO Deliang;LIAO Duanfang;FU Ronggeng(School of Pharmacy,Hunan University of Chinese Medicine,Changsha,Hunan 410208,China;State Key Laboratory ofChinese Medicine Powder and Medicine Innovation in Hunan（Incubation）,Hunan University of Chinese Medicine,Changsha,Hunan 410208,China;Hunan Provincial Key Laboratory of Diagnostic and Research in Chinese Medicine,Hunan Universityof Chinese Medicine,Changsha,Hunan 410208,China)

机构地区：[1]湖南中医药大学药学院,湖南长沙410208 [2]湖南中医药大学中药粉体与创新药物省部共建国家重点实验室培育基地,湖南长沙410208 [3]国家重点学科国家中医药管理局病理生理实验室,湖南长沙410208

出　　处：《湖南中医药大学学报》2018年第6期614-618,共5页Journal of Hunan University of Chinese Medicine

基　　金：国家自然科学基金面上项目(81472465);湖南省自然科学基金项目(2015JJ6085);湖南省教育厅资助科研项目(13B080);2015药学湖南省重点学科开放基金项目;2015中医药国际合作专项基金资助项目(ZYGZ201502);湖南中医药大学本科教学质量工程项目(ZY-005)

摘　　要：目的基于分子对接探讨水杨酰苯胺化合物Ⅰ-Ⅳ与代谢型谷氨酸受体5(metabotropic glutamate receptor 5,mglu5)之间的相互作用并测定化合物Ⅰ-Ⅳ的体外抗肝癌HepG2细胞增殖活性。方法采用计算机软件,以mglu5结晶复合物5CGD为受体模板,将水杨酰苯胺化合物Ⅰ-Ⅳ进行分子对接研究;利用MTT法测定水杨酰苯胺化合物Ⅰ-Ⅳ对肝癌HepG2细胞的增殖抑制活性。结果水杨酰苯胺化合物Ⅰ-Ⅳ与mglu5的活性口袋产生疏水作用以及与活性口袋关键氨基酸残基SER809产生氢键结合;水杨酰苯胺化合物Ⅰ-Ⅳ对肝癌细胞HepG2的抗增殖活性IC50值分别为2.55μmol/L、3.99μmol/L、3.12μmol/L和7.55μmol/L。结论水杨酰苯胺化合物Ⅰ-Ⅳ与mglu5对接的结合信息有助于水杨酰苯胺类mglu5拮抗剂的结构优化和新型mglu5拮抗剂设计,该类化合物的抗肿瘤作用值得进一步研究。Objective To study the interaction between the salicylanilides Ⅰ-Ⅳ with metabotropic glutamate receptor5（mglu5） based on molecular docking and their antitumor activity in vitro. Methods The molecular docking study of salicylanilidesⅠ-Ⅳ were performed by using mglu5 as a receptor template by in silica software. In vitro cytotoxicity of salicylanilides Ⅰ-Ⅳto human hepatocellular carcinoma cell line HepG2 was measured bya MTT method. Results It was found that salicylanilides Ⅰ-Ⅳinteracted with mglu5 binding site by hydrophobic interaction anda key hydrogen bond with amino acid residue SER809. Theseinteractions were closely related to biological activity. Compounds Ⅰ-Ⅳ showed inhibitory effect on the proliferation of HepG2 cells with the IC50 values of 2.55 μM, 3.99 μmol/L, 3.12 μmol/L and 7.55 μmol/L, respectively. Conclusion The binding information ofsalicylanilides with mglu5 would be useful for modifying the structure and designing novel mglu5 antagonists. The antitumor activityof compounds of this type would be further studied.

关 键 词：水杨酰苯胺 代谢型谷氨酸受体5拮抗剂 对接 抗肿瘤 

分 类 号：R284.3[医药卫生—中药学]