QSAR and pharmacophore analysis on pyridazinone derivatives as acetylcholinesterase inhibitors

Abstract

Aim: The aim of this study is to provide a qualitative and quantitative explanation of the structure activity relationships withpharmacophore analysis and Quantitative Structure Activity Relationship (QSAR) studies of the compounds synthesized asacetylcholinesterase enzyme inhibitor by our research group.Material and Methods: Maestro 11.9 (Schrödinger, New York) was used for pharmacophore model studies. Pharmacophore analysiswas performed for all compounds showing acetylcholine esterase inhibitory effect. For QSAR studies, various physicochemicalparameters of these compounds were calculated using GaussView 5.0 and ChemDraw 15.0 programs. Regression analysis wasperformed by using these parameters and QSAR equation was obtained.Results: All compounds overlapped and hypotheses generated. The most appropriate pharmacophore model was created bycomparing the hypothesis and activity results of the compounds. The analyses were performed using 8 different parameters for allcompounds. R2 value of equation was found 1.Conclusion: The pharmacophore analysis and the QSAR equation are applicable for all compounds synthesized as acetylcholinasteraseinhibitory and containing pyridazinon-2-ylacetohydrazide structure. Also, the estimated IC50 values can be calculated before thecompounds are synthesized using the QSAR equation.