Synthesis of N-(5,7-diamino-3-phenyl-quinoxalin-2-yl)-3,4,5-substituted anilines and N-[4[(5,7-diamino-3-phenylquinoxalin-2-yl)amino]benzoyl]-l-glutamic acid diethyl ester: evaluation of in vitro anti-cancer and anti-folate activities

Eur J Med Chem. 2008 Jan;43(1):189-203. doi: 10.1016/j.ejmech.2007.03.035. Epub 2007 Apr 18.

Abstract

Several diamino quinoxalines were designed, synthesized and evaluated as anti-tumor agents. Two compounds showed the most potent cytotoxic activities against the leukemia CCRF-CEM cell line (GI(50)<0.01microM) and the ovarian cancer cell line OVCAR-4 (GI(50)=0.03microM), respectively, with comparable/better activities than Methotrexate (MTX). Docking calculations of the complexes of hDHFR with the most active compounds identified the binding mode of the described molecules with respect to MTX.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / chemical synthesis*
  • Aniline Compounds / chemistry
  • Aniline Compounds / metabolism
  • Aniline Compounds / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Binding Sites
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Evaluation, Preclinical
  • Folic Acid Antagonists / chemical synthesis
  • Folic Acid Antagonists / chemistry
  • Folic Acid Antagonists / metabolism
  • Folic Acid Antagonists / pharmacology*
  • Glutamates / chemical synthesis*
  • Glutamates / chemistry
  • Glutamates / metabolism
  • Glutamates / pharmacology*
  • Humans
  • Kinetics
  • Models, Molecular
  • Molecular Conformation
  • Quinoxalines / chemistry*

Substances

  • Aniline Compounds
  • Antineoplastic Agents
  • Folic Acid Antagonists
  • Glutamates
  • Quinoxalines
  • glutamic acid diethyl ester
  • aniline