Synthesis of nitrated indenoisoquinolines as topoisomerase I inhibitors.
Indenoisoquinolines and dihydroindenoisoquinolines have been synthesized possessing a nitro-substituted isoquinoline ring in an effort to explore the effects of electron-withdrawing substituents on biological activity. The in vitro anticancer activities of these molecules have been tested in the National Cancer Institute's screen of 55 cell lines. The compounds have also been tested for topoisomerase I (top1) inhibition. The results indicate that these substances are a potent class of top1 inhibitors with sub-micromolar cytotoxicity mean graph midpoints (MGM) and top1 inhibition equal to camptothecin.
Morrell
Andrew
A
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907, USA.
Antony
Smitha
S
Kohlhagen
Glenda
G
Pommier
Yves
Y
Cushman
Mark
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002166:Camptothecin / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D007192:Indenes / Q000138:chemical synthesis / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007192:Indenes; D007546:Isoquinolines; D059004:Topoisomerase I Inhibitors; C039109:isoquinoline; D002166:Camptothecin