Molecular docking of 4-(2-(2-Isopropyl-5-methylphenoxy) phenoxy) phthalonitrile with Alzheimer's and COVID-19 enzymes and DFT studies

Phthalonitriles are a crucial component in the synthesis and formulation of high-performance macromolecules. Systematic theoretical study on molecular structures is essential for the rational creation of novel therapeutic compounds. This study takes aromatic nitrile type 4-(2-(2-Isopropyl-5-methylphenoxy)phenoxy)phthalonitrile (IMPN) to conduct systematic theoretical research on density functional theory (DFT) and molecular docking. The geometry-optimized structures of IMPN were examined using the DFT/B3LYP and B3PW91 methods with the 6-311G(d,p) basis set. The MEP results show that the electronic effect of methylphenoxy attracts electrons from cyano groups, which makes the cyano carbon more exposed and more prone to nucleophilic reaction. The molecular docking analysis and pharmacological potential of IMPN, as a representative pharmacologically active moiety, were assessed to ascertain its inhibitory capacity against acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) Alzheimer's and COVID-19 enzymes. IMPN, as a ligand, demonstrated effective docking scores of -8.243, -7.920, and -7.368 kcal/mol with the enzyme crystal structures.