title: Design, synthesis and biological evaluation of 3-substituted indenoisoquinoline derivatives as topoisomerase I inhibitors.
abstract: A new series of indenoisoquinoline derivatives was designed and synthesized. The in vitro anti-proliferative activity of these novel compounds was evaluated in HepG2, A549 and HCT-116 cell lines. Compounds 9a, 9b, 10a, 10c, 10e, 18a and 18b manifested potent inhibitory activity against the three tested cancer cell lines. Nineteen compounds were also tested for Top I inhibition at 50 μM. Almost all the tested compounds showed potent Top I inhibition activity at this concentration. The most potent compounds 9a and 10a demonstrated more cytotoxicity than HCPT and TPT and was comparable to CPT in inhibitory activities on Top I in our biological assay.
authors.affiliation: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
authors.forename: Xi
authors.initials: X
authors.lastname: Xu
authors.affiliation: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
authors.forename: Zhouling
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
authors.forename: Qidong
authors.initials: Q
authors.lastname: You
authors.affiliation: Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China. Electronic address: ynzhyi@sina.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China. Electronic address: zhiyuli@cpu.edu.cn.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D007546:Isoquinolines; D059004:Topoisomerase I Inhibitors; D004264:DNA Topoisomerases, Type I; C039109:isoquinoline
keywords: Anti-proliferative activity; Indenoisoquinoline derivatives; Synthesis; Top I inhibitors