IN SILICO PHARMACOPHORE VALIDATION OF ANTICONVULSANT ACTIVITY OF (E) (±)-3-MENTHONE DERIVATIVES

In an endeavor to pursuit new strategies beyond conventional ones, energetically optimized, structure based pharmacophore was used for in silico anticonvulsant screening in present investigation. The study combines pharmacophore perception with protein-ligand interactions (docking) computed by BioPredicta and MolSign of VLife Molecular Design Suite 4.3.0. We derived energy-optimized pharmacophoric features for six anticonvulsants relevant to (E)-(±) 3-menthone derivatives (J6, J14, J25, J30, J32, J33) to access novel and potent GABA-AT inhibitors. Docking produced the most cases (5/6) with score greater then Vigabatrin, a well known GABA-AT inhibitor with proven clinical anticonvulsant efficacy. The docking results suggest the probable mechanism of anticonvulsant action that leverages the strong H-bonding (LYS329ARG192A) and π-stacking interactions (PHE189A) with GABA-AT receptor. {*Corresspondence to Dr. Jainendra Jain, Principal & Professor, RamEesh Institute of Vocational and Technical Education, Greater Noida, Uttar Pradesh, India - jainendrem@gmail.com}