3D QSAR, Molecular Docking, and ADMET Studies of a Series of 2-Acetylphenol-Rivastigmine Hybrids against Monoamine Oxidase A Inhibitors

In this work, a number of 2-acetylphenol-rivastigmine hybrids have been rationally created as drugs for the treatment of behavioral disorders, especially depression. On a series of inhibitors that are 2-acetylphenol-rivastigmine hybrids, we have used virtual in silico screening techniques such as Three-dimensional QSAR, molecular docking, and pharmacokinetic properties (absorption, distribution, metabolism, excretion, and toxicity (ADMET) techniques. The aim of this study was to obtain new ligands with high inhibitory activities. The best 3D-QSAR model was created using the PLS approach and comparative molecular similarity index analysis (CoMSIA), which demonstrated strong correlative and predictive capabilities (r2 = 0.904, q2 = 0.699 and SEE = 0.094). The change of biological activity with four main components is significantly influenced by the steric, electrostatic, hydrophobic, and H-bond acceptor fields. Using these acceptable results, new molecules were developed and analyzed using in silico drug similarity, ADMET and molecular docking.