文献类型：期刊文献

中文题名：以环丙烷限制构象的新型双酰胺的设计、合成、抗癌活性及计算分析

英文题名：Design,Synthesis,Anti-cancer Activities and Computational Analysis of Novel Diamides Conformationally Restricted by Cyclopropane

作者：陈睿嘉[1];周聪[1];逄锡文[1];刘佳君[2];顾玉诚[3];刘建文[2];李忠[1]

机构：[1]华东理工大学药学院,上海市化学生物学(芳香杂环)重点实验室,上海200237;[2]华东理工大学药学院,生物反应器工程国家重点实验室&上海市新药设计重点实验室,上海200237;[3]先正达Jealott′s Hill国际研发中心,英国RG426EY

年份：2022

卷号：42

期号：1

起止页码：277

中文期刊名：有机化学

外文期刊名：Chinese Journal of Organic Chemistry

收录：CSTPCD;;Scopus;WOS:【SCI-EXPANDED(收录号:WOS:000765168000019)】；北大核心:【北大核心2020】；CSCD:【CSCD2021_2022】；

基金：Project supported by the National Key Research Program of China (No. 2017YFD0200505).

语种：中文

中文关键词：双酰胺;环丙烷;抗癌活性;靶标预测;分子对接

外文关键词：diamides;cyclopropane;anti-cancer activities;target prediction;docking

摘要：为了探索具有新型骨架的抗癌剂,设计了一系列的以环丙烷限制构象的双酰胺类化合物.大多数含有顺式环丙烷中心的外消旋体对四种肿瘤细胞系(MCF-7、BGC-823、HepG2和NCI-H460)具有良好的抑制活性.其中,消旋体顺式-N^(1)-(2-甲基-4-(全氟丙-2-基)苯基)-N^(2)-(4-苯氧基苄基)环丙烷-1,2-二羧酰胺(1-19)对MCF-7的IC_(50)值为(8.38±0.67)mg·L^(-1),显示出可进一步优化为抗癌先导物的潜力.此外,甾醇硫酸酯酶(steryl-sulfatase,STS)被PharmMapper预测为可能的靶标蛋白,并由分子对接实验进行了验证.
A series of diamides conformationally restricted by cyclopropane were designed and synthesized.Most of the racemates containing cis-cyclopropane possessed promising inhibitory activity against four cancer cell lines(MCF-7,BGC-823,HepG2 and NCI-H460).In particular,racemate cis-N^(1)-(2-methyl-4-(perfluoropropan-2-yl)phenyl)-N^(2)-(4-phenoxybenzyl)cyclopropane-1,2-dicarboxamide(1-19)showed the potential for further optimization as an anti-cancer lead with the IC_(50)value of(8.38±0.67)mg·L^(-1)on MCF-7.Moreover,steryl-sulfatase(STS)was predicated as the potential target protein and molecular docking was performed to explore the binding mode.