文献类型：期刊文献

英文题名：Synthesis and Biological Evaluation of Carbazole Aminoalcohols as Antitumor Agents

作者：Chen, Zhuo[1];Yang, Tingyuan[1];Wang, Weisi[2];Yao, Junmin[2];Han, Shaomin[1];Tao, Yi[2];Wang, Rui[1];Duan, Liping[2,3,4]

机构：[1]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, Shanghai 200237, Peoples R China;[2]Chinese Minist Hlth, WHO Collaborating Ctr Malaria Schistosomiasis & F, Chinese Ctr Dis Control & Prevent, Key Lab Parasitol & Vector Biol,Natl Inst Parasit, Shanghai 200025, Peoples R China;[3]Xinjiang Med Univ, Affiliated Hosp 1, State Key Lab Incubat Base Xinjiang Major Dis Res, Clin Med Res Inst, Urumqi 830054, Peoples R China;[4]Qinghai Prov Peoples Hosp, Xining 810007, Qinghai, Peoples R China

年份：2018

卷号：3

期号：44

起止页码：12630

外文期刊名：CHEMISTRYSELECT

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000452173000032)】；

基金：This work is financially supported by the Fundamental Research Funds for the Central Universities, the National Natural Science Foundation of China (Grants Nos. 21302054 and 21502181) (Z.C. and W.W.), the Shanghai Committee of Science and Technology (Grant No. 13ZR1453100) (Z.C.), 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：Apoptosis; Bcl-2; Carbazole aminoalcohols; Topoisomerase I (topo I)

摘要：A series of racemic and chiral carbazole aminoalcohols were synthesized and evaluated of their antitumor activities. The heterocycle, substitution site, length of alkyl chain as well as chirality were proved to interfere the topoisomerase I (topo I) inhibition activities. Carbazole aminoalcohols with potent topo I inhibition activities, like pyrrolidine derivative 5 and propyl- to pentyl- amines derivatives 7, 14, 15 and 24, were proved to exhibit good antitumor activities with IC(50)s in the single digit micromolar range against cancer cell lines A549, HCT116, and MDA-MB-231. Meanwhile, the hexyl- to decyl- amines substituted carbazole aminoalcohols (16-22), though not showing good topo I inhibition activities, were also found to have potent antitumor activities. Further research proved that the representative compound 16 had broad-spectrum antitumor activities against 15 cancer cell lines from various organs with IC(50)s at 1.5 - 7.9 mu M and induced apoptosis-inducing activities in leukemia cell lines. In in vivo studies, 16 inhibits the tumor growth in OCI-AML2 xenograft model with TGI = 43%. Bcl-2 was proved to involve in compound 16 induced apoptosis.