8,9-methylenedioxybenzo[i]phenanthridines: topoisomerase I-targeting activity and cytotoxicity.
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.
Li
Dajie
D
Department of Pharmaceutical Chemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020, USA.
Zhao
Baoping
B
Sim
Sai-Peng
SP
Li
Tsai-Kun
TK
Liu
Angela
A
Liu
Leroy F
LF
LaVoie
Edmond J
EJ
D002455:Cell Division; D004247:DNA / Q000378:metabolism; D006801:Humans; D010617:Phenanthridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors
D010617:Phenanthridines; D059004:Topoisomerase I Inhibitors; D004247:DNA