3D-QSAR and docking study of 2-((pyridin-3-yloxy)methyl) piperazines as α7 nicotinic acetylcholine receptor modulators for the treatment of inflammatory disorders.

3D-QSAR and docking study of 2-((pyridin-3-yloxy)methyl) piperazines as α7 nicotinic acetylcholine receptor modulators for the treatment of inflammatory disorders. Mini Rev Med Chem. 2019 Sep 04;: Authors: Purohit D, Saini V, Kumar S, Kumar A, Narasimhan B Abstract Comparative molecular field analysis (CoMFA) of 27 analogues of 2-((pyridin-3-yloxy)methyl)piperazine derivatives was carried out using software Tripos SYBYL X. Optimal r2 (0.854) and q2 (0.541) values were obtained for developed 3D QSAR model. The contour plots obtained from CoMFA analysis have shown 13.84% steric contribution and 66.14% electrostatic contribution towards anti-inflammatory activity. The homology model of the receptor protein, α7 nicotinic acetylcholine, was generated in SWISS MODELLER using auto template mode and was analysed for the quality using Procheck, QMEAN Z-score, Anolea and GROMOS plots. The QMEAN score for the model was observed to be -3.862. The generated model of alpha 7 nicotinic acetylcholine receptor was used for docking study of 27 piperazine analogues using Auto-Dock 4.2.5.1. The dock score obtained from docking analysis was then correlated with experimental pIC50 values for in-silico validation of the developed CoMFA model and a good correlation was obtained with correlation coefficient (r2) value of -0.7378. The present investigation suggests an optimal 3D-QSAR with CoMFA model for further evaluating new chemical entities based on pip...
Source: Mini Reviews in Medicinal Chemistry - Category: Chemistry Authors: Tags: Mini Rev Med Chem Source Type: research