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Synthesis and Biological Evaluation of Carbazole Aminoalcohols as Antitumor Agents
Author(s) -
Chen Zhuo,
Yang Tingyuan,
Wang Weisi,
Yao Junmin,
Han Shaomin,
Tao Yi,
Wang Rui,
Duan Liping
Publication year - 2018
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201803029
Subject(s) - carbazole , chemistry , stereochemistry , apoptosis , in vivo , alkyl , topoisomerase , cell culture , leukemia , chirality (physics) , pyrrolidine , in vitro , biochemistry , biology , organic chemistry , immunology , genetics , chiral symmetry breaking , microbiology and biotechnology , physics , quantum mechanics , nambu–jona lasinio model , quark
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 μΜ 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.