title: Dihydroindenoisoquinolines function as prodrugs of indenoisoquinolines.
abstract: Dihydroindenoisoquinolines are analogs of cytotoxic indenoisoquinoline topoisomerase I (Top1) inhibitors, exhibiting potent cytotoxicity but weak inhibitory activity toward Top1. Through COMPARE analysis, cytotoxicity studies in Top1-deficient cells, chemical synthesis and biological evaluation of methylated dihydroindenoisoquinoline 5, we demonstrated that dihydroindenoisoquinolines function as prodrugs of indenoisoquinolines in cancer cells.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Xiangshu
authors.initials: X
authors.lastname: Xiao
authors.forename: Ze-Hong
authors.initials: ZH
authors.lastname: Miao
authors.forename: Smitha
authors.initials: S
authors.lastname: Antony
authors.forename: Yves
authors.initials: Y
authors.lastname: Pommier
authors.forename: Mark
authors.initials: M
authors.lastname: Cushman
mesh_terms: D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D011355:Prodrugs / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D007546:Isoquinolines; D011355:Prodrugs