新型含咔唑环酰腙衍生物的合成及Cdc25B/PTP1B抑制活性评价  

Synthesis and Cdc25B/PTP1B Inhibitory Activity Evaluation of Novel Acylhydrazone Derivatives Containing Carbazole Moity

作　　者：李英俊[1] 王思远[1] 靳焜[2] 高立信 盛丽 张楠[1] 刘季红[4] 李佳 Li Yingjun;Wang Siyuan;Jin Kun;Gao Lixin;Sheng Li;Zhang Nan;Liu Jihong;Li Jia(College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029;State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116012;State Key Laboratory of Drug Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203;Chemistry Analysis & Research Center, Faculty of Chemical, Environmental & Biological Science and Technology, Dalian University of Technology, Dalian 116023)

机构地区：[1]辽宁师范大学化学化工学院,大连116029 [2]大连理工大学精细化工国家重点实验室,大连116012 [3]中国科学院上海药物研究所国家新药筛选中心药物研究国家重点实验室,上海201203 [4]大连理工大学化环生学部分析测试中心,大连116023

出　　处：《有机化学》2019年第2期491-499,共9页Chinese Journal of Organic Chemistry

基　　金：辽宁省自然科学基金(No.20102126)资助项目~~

摘　　要：以咔唑和4-氰基氯化苄为初始原料,经多步反应合成出了一系列新型含咔唑基团的酰腙衍生物6,并利用IR、^1H NMR、^13C NMR和元素分析对其进行了结构表征.对目标化合物进行了Cdc25B/PTP1B抑制活性评价,结果显示,目标化合物6对Cdc25B/PTP1B均具有较高的抑制活性,其中4-[(咔唑-9-基)甲基]-N'-(2-羟基-1-萘亚甲基)苯甲酰肼(6g)对Cdc25B和PTP1B的抑制活性最高,IC50值分别为(2.16±0.38)和(1.06±0.23)μg/mL.对化合物6g进行分子对接的研究结果表明,6g能与Cdc25B/PTP1B酶形成稳定的复合物,形成氢键和疏水等相互作用.A series of novel acylhydrazone derivatives 6 containing carbazole moity were synthesized by carbazole and 4-cyanobenzyl chloride as starting materials via multi-step reactions. Their structures were characterized by IR, ^1H NMR, ^13C NMR spectra and elemental analysis. All synthesized target compounds were evaluated for the inhibitory activities against Cdc25B and PTP1B. The results show that the target compounds display significant inhibitory activities against Cdc25B/PTP1B. Among them, compound 4-((carbazol-9-yl)methyl)-N'-(2-hydroxy-1-naphthalenylmethylene)benzoyl hydrazide (6g) had the highest inhibitory activities against Cdc25B and PTP1B with IC50 values of (2.16±0.38) and (1.06±0.23) μg/mL, respectively. The molecular docking results indicated that the hydrogen bond and hydrophobic interaction formed between compound 6g and Cdc25B/PTP1B enzyme.

关 键 词：酰腙 咔唑 合成 Cdc25B和PTP1B抑制剂 分子对接 

分 类 号：TQ460.1[化学工程—制药化工]