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.

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.

• Authors: Paola Corona, Mario Loriga, M Paola Costi, Stefania Ferrari, Giuseppe Paglietti
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 43 Issue 1 Pg. 189-203 (Jan 2008) ISSN: 0223-5234 [Print] France
• PMID: 17532099 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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