Docking and QSAR studies of β-phenylethylidenehydrazine derivatives as a Gamma-aminobutyric acid aminotransferase inhibitor

beta-Phenylethylidenehydrazine (PEH) derivatives have been recognized as Gamma-aminobutyric acid aminotransferase (GABA-AT) inhibitors. In this research a group of newly synthesized of PEH analogs, possessing a variety of substituents (Me, OMe, Cl, and CF(3)) at the 2-, 3-, and 4-position of the phenyl ring, were subjected to docking study and quantitative structure activity relationship (QSAR) analysis. PEH analogs were built by HYPERCHEM program, and conformational studies were performed through semi-empirical method followed by PM3 method. QSAR descriptors were obtained from the EDRAGON and HYPERCHEM, and equations were derived from multilinear regression (MLR) method. The sums of the JGI2, H6m, and E2s were identified as the most significant descriptors. This simple equation can be used to estimate the GABA-AT inhibitory activity for new derivatives of this series of compounds. Docking study was performed by using AutoDock4 program on the all compounds. The obtained results show that the phenyl ring is inserted into the lipophilic pocket and that the NHNH(2) moiety is situated in a mainly polar region of the enzyme. These computational studies can offer some useful references for understanding the action mechanism and performing the molecular design or modification of this series of GABA-AT inhibitors.