Grid potential analysis, virtual screening studies and ADME/T profiling on N‐arylsulfonylindoles as anti‐HIV‐1 agents

Abstract

A grid potential analysis employing a novel approach of 3D quantitative structure–activity relationships (QSAR) as AutoGPA module in MOE2009.10 was performed on a dataset of 42 compounds of N‐arylsulfonylindoles as anti‐HIV‐1 agents. The uniqueness of AutoGPA module is that it automatically builds the 3D‐QSAR model on the pharmacophore‐based molecular alignment. The AutoGPA‐based 3D‐QSAR model obtained in the present study gave the cross‐validated Q2 value of 0.588, r2pred value of 0.701, r2m statistics of 0.732 and Fisher value of 94.264. The results of 3D‐QSAR analysis indicated that hydrophobic groups at R1 and R2 positions and electron releasing groups at R3 position are favourable for good activity. To find similar analogues, virtual screening on ZINC database was carried out using generated AutoGPA‐based 3D‐QSAR model and showed good prediction. In addition to those mentioned earlier, in‐silico ADME absorption, distribution, metabolism and excretion profiling and toxicity risk assessment test was performed, and results showed that majority of compounds from current dataset and newly virtually screened hits generated were within their standard limit. Copyright © 2013 John Wiley & Sons, Ltd.