文献类型：期刊文献

英文题名：Carbazole Aminoalcohols Induce Antiproliferation and Apoptosis of Human Tumor Cells by Inhibiting Topoisomerase I

作者：Wang, Weisi[1,3];Sun, Xiao[2];Sun, Deheng[2];Li, Shizhu[1];Yu, Yang[2];Yang, Tingyuan[2];Yao, Junmin[1];Chen, Zhuo[2];Duan, Liping[1]

机构：[1]Chinese Minist Hlth, WHO Collaborating Ctr Malaria Schistosomiasis & F, Chinese Ctr Dis Control & Prevent, Natl Inst Parasit Dis,Key Lab Parasitol & Vector, Shanghai 200025, Peoples R China;[2]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, Shanghai 200237, Peoples R China;[3]Zhejiang Univ, ZJU ENS Joint Lab Med Chem, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China

年份：2016

卷号：11

期号：24

起止页码：2675

外文期刊名：CHEMMEDCHEM

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000391292900005)】；

基金：This work was supported financially by the Fundamental Research Funds for the Central Universities (China), the National Natural Science Foundation of China (Grant Nos. 21302054 and 21502181; Z.C. and W.W.), the Shanghai Committee of Science and Technology (Grant No. 13ZR1453100; Z.C.), and the Opening Fund of Shanghai Key Laboratory of Chemical Biology (Grant No. SKLCB-2012-05; Z.C.).

语种：英文

外文关键词：antitumor agents; apoptosis; carbazole aminoalcohols; cell-cycle arrest; topoisomerase

摘要：Novel carbazole aminoalcohols were designed and synthesized as anticancer agents. Among them, alkylamine-chain-substituted compounds showed the most promising antiproliferative activity, with IC50 values in the single-digit micromolar range against two human tumor cell lines. Topoisomerase I (topo I) is likely to be one of the targets of these compounds. Results of comet assays and molecular docking indicate that the representative compounds may act as topoI poisons, causing single-strand DNA damage by stabilizing the topo I-DNA cleavage complex. In particular, the most potent compound, 1-(butylamino)- 3-(3,6-dichloro-9H-carbazol-9-yl) propan-2-ol (6), was shown to be able to induce G2-phase cell-cycle arrest and apoptosis in HeLa cells.