5-substituted 2-bromoindolo[3,2-b]quinoxalines. A class of potential antitumor agents with cdc25 phosphatase inhibitory properties

Arch Pharm (Weinheim). 1998 Nov;331(11):352-8. doi: 10.1002/(sici)1521-4184(199811)331:11<352::aid-ardp352>3.0.co;2-2.

Abstract

Several derivatives of 5-substituted 2-bromoindolo[3,2-b]quinoxaline were synthesized and characterized. The synthesized compounds were evaluated for their antitumor activity using the National Cancer Institute-in vitro-disease oriented antitumor screen and two biochemical mechanism-based screens (cdc2 kinase and cdc25 phosphatase). Compound 19 showed broad spectrum antitumor activity with full panel (MG-MID) GI50. TGI, and LC50 of 14.2, 31.6- and 66.2 microM, respectively. In addition it inhibited cdc2 kinase and cdc25 phosphatase with IC50's of 70 and 25 microM, respectively. Thus, compound 19 represents a model for compounds with potential antitumor activity and cdc25 phosphatase inhibitory properties.

Publication types

  • Comparative Study

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use*
  • Female
  • Humans
  • Male
  • Phosphoric Monoester Hydrolases / antagonists & inhibitors*
  • Quinoxalines / chemical synthesis*
  • Quinoxalines / chemistry
  • Quinoxalines / therapeutic use*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured / drug effects*

Substances

  • Antineoplastic Agents
  • Quinoxalines
  • Phosphoric Monoester Hydrolases