Molecular Docking Structure-Activity Relationship, ADMET Evaluation and Pharmacokinetics Studies of Anti-HIV Agents and Methyl-Diarylpyrimidines Non-Nucleoside Reverse Transcriptase Inhibitors

In this study, the interaction between human immunodeficiency virus reverse transcriptase and methyldiarylpyrimidines containing a hydroxyimino, hydrazine, hydroxyl, cyclopropylamino, cyano or chloro etc. substituent was studied by molecular docking simulation, accomplished with AutoDock4.2 absorption, distribution, metabolism, excretion toxicity-structure-activity relationship Swiss metabolism servers were used to predict pharmacokinetics toxicity properties of all compounds. As result, analysis revealed that there are extensive interactions diarylpyrimidine derivatives Lys101, Tyr188, Val179, Lys103, Glu138, Leu234, Phe227 Trp229 residues in active site virus-1 transcriptase. The formation hydrogen bonds diarylpyrimidines Lys101 Glu138 play important roles inhibiting activity virus. All compounds respect conditions mentioned Lipinski’s rule have acceptable properties. preliminary structure-activity also investigated. A structureactivity these target molecules highlighted preference for smaller more flexible group’s substitution linker left ring pyrimidine skeleton enhancing anti-human activity. acrylonitrile C4-substituent substantially improved potency against wild-type several mutant strains, 2nd position is most preferred improve antiviral This information might be helpful further optimizations.