Dihydroindenoisoquinolines function as prodrugs of indenoisoquinolines.
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.
Xiao
Xiangshu
X
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Purdue University, West Lafayette, IN 47907, USA.
Miao
Ze-Hong
ZH
Antony
Smitha
S
Pommier
Yves
Y
Cushman
Mark
M
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*
D007546:Isoquinolines; D011355:Prodrugs