11-Substituted 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine derivatives as novel topoisomerase I-targeting agents.
Several 11-substituted benzo[i]phenanthridine derivatives were synthesized, and their TOP1-targeting activity and cytotoxicity were assessed. Comparative data indicate that TOP1-targeting was often the primary molecular target associated with their cytotoxicity. Several 11-aminoalkyl derivatives, 11-aminocarboxy derivatives as well as the 11-[(2-dimethylamino)ethyl]carboxamide of 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine were synthesized and did exhibit considerable cytotoxicity with IC(50) values ranging from 20 to 120 nM in the human lymphoblast tumor cell line RPMI8402.
Feng
Wei
W
Department of Pharmaceutical Chemistry, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854-8020, USA.
Satyanarayana
Mavurapu
M
Tsai
Yuan-Chin
YC
Liu
Angela A
AA
Liu
Leroy F
LF
LaVoie
Edmond J
EJ
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007945:Leukemia, Lymphoid / Q000378:metabolism / Q000473:pathology*; D010617:Phenanthridines / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D010617:Phenanthridines; D059004:Topoisomerase I Inhibitors; D004264:DNA Topoisomerases, Type I
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