Design, synthesis and biological evaluation of 2-mercapto-3-phenethylquinazoline bearing anilide fragments as potential antitumor agents: molecular docking study

Bioorg Med Chem Lett. 2013 Jul 1;23(13):3935-41. doi: 10.1016/j.bmcl.2013.04.056. Epub 2013 Apr 29.

Abstract

A novel series of 2-(3-phenethyl-4(3H)quinazolin-2-ylthio)-N-substituted anilide and substituted phenyl 2-(3-phenethyl-4(3H) quinazolin-2-ylthio)acetate were designed, synthesized and evaluated for their in-vitro antitumor activity. Compound 15 possessed remarkable broad-spectrum antitumor activity which almost sevenfold more active than the known drug 5-FU with GI50 values of 3.16 and 22.60 μM, respectively. Compound 15 exhibited remarkable growth inhibitory activity pattern against renal cancer (GI50=1.77 μM), colon cancer (GI50=2.02 μM), non-small cell lung cancer (GI50=2.04 μM), breast cancer (GI50=2.77 μM), ovarian cancer (GI50=2.55 μM) and melanoma cancer (GI50=3.30 μM). Docking study was performed for compound 15 into ATP binding site of EGFR-TK which showed similar binding mode to erlotinib.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anilides / chemistry*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Quinazolines / chemical synthesis
  • Quinazolines / chemistry
  • Quinazolines / pharmacology*
  • Structure-Activity Relationship
  • Sulfhydryl Compounds / chemical synthesis
  • Sulfhydryl Compounds / chemistry
  • Sulfhydryl Compounds / pharmacology*

Substances

  • Anilides
  • Antineoplastic Agents
  • Quinazolines
  • Sulfhydryl Compounds