8,9-Methylenedioxybenzo[i]phenanthridines_ Topoisomerase I-Targeting activity and cytotoxicity

• Main Authors: Li, D., Zhao, B., Sim, S.P, Li, T.K, Liu, A., Liu, L.F., LaVoie, E.J.
• Format: Article
• Language: English
• Published: Elsevier Ltd 2003
• Subjects: QD Chemistry; R Medicine (General)
• Online Access: http://ir.unimas.my/id/eprint/2199/1/Bioorganic.pdf; http://ir.unimas.my/id/eprint/2199/; http://www.sciencedirect.com/science/article/pii/S0968089603003948

Substituted benzo[i]phenanthridines that have incorporated within their structure an 8,9-methylenedioxy group can exhibit topoisomerase I-targeting activity. Structure–activity studies were performed to examine the influence of saturation at the 11,12-positions of several substituted 8,9-methylenedioxybenzo[i]phenanthridines. The activities of these dihydro analogues were compared to those of their unsaturated analogues. In addition, the influence of varying substituents at the 2- and 3-positions within the A-ring of these 8,9-methylenedioxybenzo[i]phenanthridines on their relative potency as topoisomerase I-targeting agents and cell proliferation as determined using the MTT assay was investigated. 2,3-Dimethoxy-8,9 Methylenedioxybenzo[i]phenanthridine and its 11,12-dihydro derivative were among the more potent analogues evaluated with regard to topoisomerase I-targeting activity and cytotoxicity.