Dimethoxybenzo[i]phenanthridine-12-carboxylic acid derivatives and 6H-dibenzo[c,h][2,6]naphthyridin-5-ones with potent topoisomerase I-targeting activity and cytotoxicity.
The exceptional TOP1-targeting activity and antitumor activity of ARC-111, 1, prompted studies on similarly substituted benzo[i]phenanthridine-12-carboxylic ester and amide derivatives. These studies were extended to include 6-substituted 8,9-dimethoxy-2,3-methylenedioxy-dibenzo[c,h][2,6]naphthyridin-5-ones, which represent reversed lactam analogues of 1. Several of these analogues retained the potent TOP1-targeting activity and cytotoxicity observed for ARC-111.
Department of Pharmaceutical Chemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020, USA.
Alexander L
AL
Ruchelman
Shejin
S
Zhu
Nai
N
Zhou
Angela
A
Liu
Leroy F
LF
Liu
Edmond J
EJ
LaVoie
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009287:Naphthyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010617:Phenanthridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors
D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D009287:Naphthyridines; D010617:Phenanthridines; D059004:Topoisomerase I Inhibitors; C497757:dimethoxybenzo(i)phenanthridine-12-carboxylic acid; C481982:topovale