title: Synthesis and crystal structure of new temephos analogues as cholinesterase inhibitor: molecular docking, QSAR study, and hydrogen bonding analysis of solid state.
abstract: A series of temephos (Tem) derivatives were synthesized and characterized by 31P, 13C, and 1H NMR and FT-IR spectral techniques. Also, the crystal structure of compound 9 was investigated. The hydrogen bonding energies (E2) 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═S moiety were higher than those with a P═O 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 q2=0.965 between the training and testing sets.
authors.affiliation: Department of Chemistry, Tarbiat Modares University , P.O. Box 14115-175, Tehran, Iran.
authors.forename: Khodayar
authors.initials: K
authors.lastname: Gholivand
authors.forename: Ali Asghar
authors.initials: AA
authors.lastname: Ebrahimi Valmoozi
authors.forename: Mahyar
authors.initials: M
authors.lastname: Bonsaii
mesh_terms: D001665:Binding Sites; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D003460:Crystallization; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D021281:Quantitative Structure-Activity Relationship; D000002:Temefos / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D002800:Cholinesterase Inhibitors; D000002:Temefos