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

  • Bioorg Med Chem Lett. 2004 Nov 15;14(22):5585-9. doi: 10.1016/j.bmcl.2004.08.070.
Alexander L Ruchelman  1 ,  Shejin Zhu ,  Nai Zhou ,  Angela Liu ,  Leroy F Liu ,  Edmond J LaVoie
Affiliations
  • 1. Department of Pharmaceutical Chemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020, USA.
PMID: 15482929 DOI: 10.1016/j.bmcl.2004.08.070
Abstract

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.