Experimental Methodologies and Evaluations of Computer-Aided Drug Design Methodologies Applied to a Series of 2-Aminothiophene Derivatives with Antifungal Activities

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.

Keywords

• 2-aminothiophene derivatives
• antifungal activity
• molecular modelling
• computer-aided drug design
• density functional theory