Molecular Surface Features in Modeling the HIV‐1 RT Inhibitory Activity of 2‐(2,6‐Disubstituted phenyl)‐3‐(substituted pyrimidin‐2‐yl)‐thiazolidin‐4‐ones

Abstract

Abstract Inhibitory activity of 2‐(2,6‐disubstituted phenyl)‐3‐(substituted pyrimidin‐2‐yl)‐thiazolidin‐4‐ones the Human Immunodeficiency Virus‐1 Reverse Transcriptase (HIV‐1 RT) have been analyzed using Combinatorial Protocol in Multiple Linear Regression (CP‐MLR) with several electronic and molecular surface area features of the compounds obtained from Molecular Operating Environment (MOE) software. The study has indicated the role of different charged molecular surface areas in modeling the inhibitory activity of the compounds. The derived models collectively suggested that the compounds should be compact without bulky substitutions on its peripheries for better HIV‐1 RT inhibitory activity. It also emphasized the necessity of hydrophobicity and compact structural features for their activity. The scope of the descriptors identified for these analogues have been verified by extending the dataset with different 2‐(disubstituted phenyl)‐3‐(substituted pyridin‐2‐yl)‐thiazolidin‐4‐ones. The joint analysis of extended dataset highlighted the information content of identified descriptors in modeling the HIV‐1 RT inhibitory activity of the compounds.