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.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Carboxylic Acids / chemical synthesis
  • Carboxylic Acids / chemistry
  • Carboxylic Acids / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Naphthyridines / chemical synthesis
  • Naphthyridines / chemistry
  • Naphthyridines / pharmacology*
  • Phenanthridines / chemical synthesis
  • Phenanthridines / chemistry
  • Phenanthridines / pharmacology*
  • Structure-Activity Relationship
  • Topoisomerase I Inhibitors*

Substances

  • Antineoplastic Agents
  • Carboxylic Acids
  • Enzyme Inhibitors
  • Naphthyridines
  • Phenanthridines
  • Topoisomerase I Inhibitors
  • dimethoxybenzo(i)phenanthridine-12-carboxylic acid
  • topovale