Molecular Docking, 3D-QSAR Studies, and In Silico ADME Prediction of p-Aminosalicylic Acid Derivatives as Neuraminidase Inhibitors

Neuraminidase (NA) is a major glycoprotein of influenza virus which is essential for viral infection. It offers a potential target for antiviral drug design and discovery. To develop novel potent neuraminidase inhibitors (NAI), Surflex-Dock was employed to dock 40 hydrophobic p-aminosalicylic acid derivatives into the active site of NA. The 3D-quantitative structure-activity relationship studies involving comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were carried out on 40 molecules. Both CoMFA (q ²=0.628, r ²=0.697) and CoMSIA (q ²=0.746, r ²=0.816) gave reasonable results. A preliminary pharmacokinetic profile of these NAI was also performed on the basis of Volsurf predictions. The results obtained from this study will be useful in the design of novel potent NAI. Novel (substituted phenyl){4-[3-(piperidin-4-yl)propyl]piperidin-1-yl} methanone derivatives were identified as potent antiproliferative agents. Compound with nitro and fluoro substitution on the phenyl ring of aryl carboxamide moiety was identified as most potent among the series to induce the apoptosis.