Design, synthesis & evaluation of condensed 2H-4-arylaminopyrimidines as novel antifungal agents

Eur J Med Chem. 2014 Apr 22:77:166-75. doi: 10.1016/j.ejmech.2014.02.066. Epub 2014 Mar 3.

Abstract

A small, focussed library of condensed 2H-4-arylaminopyrimidines, with 3-diversity points, based on an initial design by molecular docking study of this scaffold at the active site of the fungal enzyme of cytochrome P450 family, lanosterol 14α-demethylase (CYP51) was synthesized through a one-pot green chemical synthetic protocol. The screening of the synthesised compounds for antifungal activity against Candida albicans, Aspergillus fumigatus &Aspergillus niger revealed activity in many of the compounds as comparable to that of fluconazole. Based on the antifungal activity and physicochemical property data of these derivatives, a meaningful SAR has been proposed.

Keywords: Antifungal activity; Condensed pyrimidines; Docking; Lanosterol 14-α-demethylase; MWI; SAR.

MeSH terms

  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Aspergillus fumigatus / drug effects*
  • Aspergillus niger / drug effects*
  • Candida albicans / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antifungal Agents
  • Pyrimidines