Synthesis, biological evaluation, and molecular docking studies of 1,3,4-thiadiazol-2-amide derivatives as novel anticancer agents

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• 作者：Xian-Hui Yang^a ; ^&dagger ; ; ^{yangxianhui1988@126.com} ; Lu Xiang^a ; ^&dagger ; ; ^{kaka_bb@163.com} ; Xi Li^a ; ^{553289134@qq.com} ; Ting-Ting Zhao^a ; ^{changbiyuan7@163.com} ; Hui Zhang^a ; ^{zhanghui.805@163.com} ; Wen-Ping Zhou^a ; ^{wenping_zhou@163.com} ; Xiao-Ming Wang^a ; ^{xmwang@nju.edu.cn} ; Hai-Bin Gong^b ; ^{ghbxuzhou@yahoo.com.cn} ; Hai-Liang Zhu^a ; ^{zhuhl@nju.edu.cn}
• 关键词：1 ; 3 ; 4-Thiadiazol-2-amide derivatives ; Focal adhesion kinase ; Structure&ndash ; activity relationship ; Molecular docking
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2012
• 期刊代码：9_09680896
• 类别：ch
• 出版时间：1 May, 2012
• 卷：20
• 期：9
• 页码：2789-2795
• 文件大小：2213 K

摘要

A series of 1,3,4-thiadiazol-2-amide derivatives (5a-5y) have been designed and synthesized, and their biological activities were also evaluated as potential antiproliferation and FAK inhibitors. Among all the compounds, 5h showed the most potent activity in vitro, which inhibited the growth of MCF-7 and B16-F10 cell lines with IC₅₀ values of 0.45 and 0.31 渭M, respectively. Compound 5h also exhibited significant FAK inhibitory activity (IC₅₀ = 5.32 渭M). Docking simulation was performed to position compound 5h into the FAK structure active site to determine the probable binding model. The results of antiproliferative and Western-blot assay demonstrated that compound 5h possessed good antiproliferative activity. Therefore, compound 5h with potent FAK inhibitory activity may be a potential anticancer agent.