Experimental methodologies and evaluations of computer-aided drug design methodologies applied to a series of 2-aminothiophene derivatives with antifungal activities

Molecules. 2012 Feb 24;17(3):2298-315. doi: 10.3390/molecules17032298.

Abstract

Fifty 2-[(arylidene)amino]-4,5-cycloalkyl[b]thiophene-3-carbonitrile derivatives were screened for their in vitro antifungal activities against Candida krusei and Cryptococcus neoformans. Based on experimentally determined minimum inhibitory concentration (MIC) values, we conducted computer-aided drug design studies [molecular modelling, chemometric tools (CPCA, PCA, PLS) and QSAR-3D] that enable the prediction of three-dimensional structural characteristics that influence the antifungal activities of these derivatives. These predictions provide direction with regard to the syntheses of new derivatives with improved biological activities, which can be used as therapeutic alternatives for the treatment of fungal infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / pharmacology*
  • Candida / drug effects
  • Computer Simulation
  • Computer-Aided Design*
  • Cryptococcus neoformans / drug effects
  • Drug Design*
  • Inhibitory Concentration 50
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Nitriles / pharmacology*
  • Principal Component Analysis
  • Quantitative Structure-Activity Relationship
  • Regression Analysis
  • Surface Properties
  • Thiophenes / pharmacology*

Substances

  • Antifungal Agents
  • Nitriles
  • Thiophenes