Molecular Docking and QSAR Studies: Noncovalent Interaction between Acephate Analogous and the Receptor Site of Human Acetylcholinesterase

Twelve new compounds of acephate (Ace) analogues were synthesized and characterized by 31P, 13C, and 1H NMR and IR spectroscopy. The probable insecticide potential of these compounds as well as 23 previously prepared molecules with a general skeleton of RC(O)–NH–P(O)X1X2 was predicted by PASS software. Docking analysis showed that hydrophobic interaction and hydrogen bonding were created between the functional groups of Ace derivatives and the receptor sites of acetylcholinesterase. PCA–QSAR indicated that the electronic descriptors are dominated in comparison with the structural descriptors. The experimental–QSAR (R2 = 0.903 and VIF < 2.997) and DFT–QSAR (R2 = 0.990 and VIF ≤ 10) models clarified that the net charge of functional groups contributes an important function in an inhibition mechanism. Validity and integrity of this model were confirmed by the LOO cross-validation method with q2 = 0.940 and low residuals between the training and testing sets. The correlation matrix of DFT–QSAR model confirmed the molecular docking results.