Gholivand_2014_J.Agric.Food.Chem_62_5761

A series of temephos (Tem) derivatives were synthesized and characterized by (31)P, (13)C, and (1)H NMR and FT-IR spectral techniques. Also, the crystal structure of compound 9 was investigated. The hydrogen bonding energies (E(2)) were calculated by NBO analysis of the crystal cluster. The activities and the mixed-type mechanism of Tem derivatives were evaluated using the modified Ellman's and Lineweaver-Burk's methods on cholinesterase (ChE) enzymes. The inhibitory activities of Tem derivatives with a P horizontal lineS moiety were higher than those with a P horizontal lineO moiety. Docking analysis disclosed that the hydrogen bonds occurred between the OR (R = CH3 and C2H5) oxygen and N-H nitrogen atoms of the selected compounds and the receptor site (GLN and GLU) of ChEs. PCA-QSAR indicated that the correlation coefficients of the electronic variables were dominant compared to the structural descriptors. MLR-QSAR models clarified that the net charges of nitrogen and phosphorus atoms contribute important electronic function in the inhibition of ChEs. The validity of the QSAR model was confirmed by a LOO cross-validation method with q(2) = 0.965 between the training and testing sets.