Carbazole Aminoalcohols Induce Antiproliferation and Apoptosis of Human Tumor Cells by Inhibiting Topoisomerase I

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 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‐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. Under arrest: Carbazole aminoalcohols were synthesized and tested for their inhibitory potential against topoisomerase I (topo 1) and for their antiproliferative activity against human tumor cell lines. Structure–activity relationships indicated that alkylamine‐substituted compounds exhibit the most efficient antiproliferative activity, in agreement with their topo I inhibitory capacity. Further studies confirmed that the most potent compound induces G2‐phase cell‐cycle arrest and apoptosis in HeLa cells.