title: Synthesis and biological evaluations of novel indenoisoquinolines as topoisomerase I inhibitors.
abstract: A series of novel indenoisoquinoline derivatives were synthesized. The anticancer activities of these molecules were tested in human cancer cell lines A549, HepG2, and HCT-116. These compounds were also tested for their activity of topoisomerase I (top1) inhibition. Among them, compound 25 was found to be 10-times more potent in cell-killing activity for both cell lines HepG2 and HCT-116 than reported compound 11, with IC(50) of 0.019 and 0.093μM, respectively. Compound 25 was also found to have stronger top1 inhibition activity than 11 in our inhibition assay. Further in vivo evaluations of compound 25 are in progress and will be reported in due course.
authors.affiliation: Department of Medicinal Chemistry, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Zhang
authors.forename: Rubing
authors.initials: R
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.forename: Na
authors.initials: N
authors.lastname: Lu
authors.forename: Jubo
authors.initials: J
authors.lastname: Wang
authors.forename: Qidong
authors.initials: Q
authors.lastname: You
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Li
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Guo
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D007546:Isoquinolines; D059004:Topoisomerase I Inhibitors; D004264:DNA Topoisomerases, Type I