12-Substituted 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridines as novel topoisomerase I-targeting antitumor agents.
2,3-Dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine and a few of its 12-substituted analogs are active as TOP1-targeting agents. Studies were performed to further evaluate the potential of this series of non-camptothecin TOP1-targeting agents. The influence of a hydroxymethyl, formyl, N,N-dimethylaminomethyl, 2-(N,N-dimethylamino)ethyl, 3-(N,N-dimethylamino)propyl), and 4-(N,N-dimethylamino)butyl substituent at the 12-position on TOP1-targeting activity and tumor cell growth was evaluated. In addition, the relative pharmacologic activities of the 12-carboxamide analog, as well as its N-methyl and N,N-dimethyl derivatives were assessed.
Feng
Wei
W
Department of Medicinal Chemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020, USA.
Satyanarayana
Mavurapu
M
Tsai
Yuan-Chin
YC
Liu
Angela A
AA
Liu
Leroy F
LF
LaVoie
Edmond J
EJ
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D006801:Humans; D010617:Phenanthridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D059004:Topoisomerase I Inhibitors
D000970:Antineoplastic Agents; D010617:Phenanthridines; D059004:Topoisomerase I Inhibitors; D004264:DNA Topoisomerases, Type I