title: Carbazole Aminoalcohols Induce Antiproliferation and Apoptosis of Human Tumor Cells by Inhibiting Topoisomerase I.
abstract: Novel carbazole aminoalcohols were designed and synthesized as anticancer agents. Among them, alkylamine-chain-substituted compounds showed the most promising antiproliferative activity, with IC50values 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.
authors.affiliation: National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, WHO Collaborating Centre for Malaria, Schistosomiasis, and Filariasis, Key laboratory of Parasitology and Vector Biology of the Chinese Ministry of Health, Shanghai, 200025, China.|ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Weisi
authors.initials: W
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Sun
authors.affiliation: Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Deheng
authors.initials: D
authors.lastname: Sun
authors.affiliation: National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, WHO Collaborating Centre for Malaria, Schistosomiasis, and Filariasis, Key laboratory of Parasitology and Vector Biology of the Chinese Ministry of Health, Shanghai, 200025, China.
authors.forename: Shizhu
authors.initials: S
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Tingyuan
authors.initials: T
authors.lastname: Yang
authors.affiliation: National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, WHO Collaborating Centre for Malaria, Schistosomiasis, and Filariasis, Key laboratory of Parasitology and Vector Biology of the Chinese Ministry of Health, Shanghai, 200025, China.
authors.forename: Junmin
authors.initials: J
authors.lastname: Yao
authors.affiliation: Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Chen
authors.affiliation: National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, WHO Collaborating Centre for Malaria, Schistosomiasis, and Filariasis, Key laboratory of Parasitology and Vector Biology of the Chinese Ministry of Health, Shanghai, 200025, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Duan
mesh_terms: D000438:Alcohols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002227:Carbazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000438:Alcohols; D000588:Amines; D000970:Antineoplastic Agents; D002227:Carbazoles; D059004:Topoisomerase I Inhibitors; D004264:DNA Topoisomerases, Type I
keywords: antitumor agents; apoptosis; carbazole aminoalcohols; cell-cycle arrest; topoisomerase I