GABA-AT INHIBITORY ACTIVITY OF BENZOTHIAZOLE – GABA ANALOGS: IN-SILICO APPROACH FOR ANTIEPILEPTIC PROFILEAbstract
Estimation of binding affinity of receptor – ligand complex in docking study of small molecules plays an Important role in structure based drug development process. The γ-amino-butyric acid amino-transferase (GABA-AT) exhibits a catalytic role in regulating γ-amino -butyric acid (GABA) level in brain and responsible for many physiological and pathological changes. Here, in – silico study of benzothiazoles – GABA analogs as γ-amino-butyric acid amino-transferase inhibitors for antiepileptic activity was done. Docking study was completed by AutoDock Vina 1.1.2 (MGI Tools 1.5.6) and PyMol 1.7. We derived energy optimized pharmacophoric features for eighty five ligands and; compared with carbamazepine and vigabatrine. Docking results reveal that most of the ligands showed more affinity (-10.6 to -6.2 kcal/ mol) towards GABA – AT as compared to carbamazepine (-6.7 kcal/ mol) and vigabatrine (-5.0 kcal/ mol). Derivative with serial number 68 was found to possess the best binding affinity for GABA-AT with scoring energy as 10.6 kcal/ mol. Different descriptors were derived and analyzed for any violation of Lipinsky’s rule of five (Ro5) of the designed derivatives.
J. Gagoria * and P. K. Verma
Pharmaceutical Chemistry Division, Faculty of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, Haryana, India.
26 May, 2016
25 June, 2016
28 September, 2016
01 November, 2016