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Carbazole Aminoalcohols Induce Antiproliferation and Apoptosis of Human Tumor Cells by Inhibiting Topoisomerase I
Author(s) -
Wang Weisi,
Sun Xiao,
Sun Deheng,
Li Shizhu,
Yu Yang,
Yang Tingyuan,
Yao Junmin,
Chen Zhuo,
Duan Liping
Publication year - 2016
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201600391
Subject(s) - apoptosis , carbazole , topoisomerase , chemistry , cancer research , programmed cell death , microbiology and biotechnology , pharmacology , biology , biochemistry , in vitro , organic chemistry
Novel carbazole aminoalcohols were designed and synthesized as anticancer agents. Among them, alkylamine‐chain‐substituted compounds showed the most promising antiproliferative activity, with IC 50 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 topo I 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‐9 H ‐carbazol‐9‐yl)propan‐2‐ol ( 6 ), was shown to be able to induce G 2 ‐phase cell‐cycle arrest and apoptosis in HeLa cells.