Molecular Docking, Synthesis and Evaluation of Antianxiety and Anticonvulsant potential of some Novel 3-(substituted benzylidene)-5-phenyl-7-nitro-1, 3-dihydro-1H, 3H-1,4-Benzodiazepine-2-one

The given title proposed with the aim to synthesize some novel benzylidene substituted benzodiazepine analogue to evaluate GABAA receptor inhibitory activity. Molecular docking simulation studies were also performed on life molecular suite software. All compounds found to possess good dock score, but varied in formation of intermolecular complexes at the receptor site. Bonding interactions like hydrogen bonds, hydrophilic bonds and pi-interactions of the ligand library with receptor binding site were considered as parameter for synthesis of selected and potent molecules. Diazepam to be selected as the reference compound and included in ligand library to ran simultaneously. Diazepam found to develop two hydrogen bonds with TYR 106A amino acid residue whereas π-π stacking interaction with TYR 106A and PHE 3A protein moiety. It is capable to form hydrophobic interactions with PHE 104A, PHE 3A, VAL 4A, ILE 32A, TYR 6A, TYR 5A, LYS 6A, and ARG 14A.  Most of the proposed compounds interacted in similar manner as diazepam. Dock score of diazepam and tested compounds were also comparable. All the synthesized molecules were characterized by IR, 1H-NMR and Mass spectrometric data. Elevated plus maze test and Maximal electroshock methods were selected to evaluate antianxiety and anticonvulsant activity respectively. Substitution of methoxy, ethoxy and dimethyl amino groups on benzylidene benzene found to have much therapeutic value but halogen and nitro substitution were not active even unable to show interaction forces with target receptor. Isopropyl group also found to possess potential effect on CNS.