Synthesis, characterization, and biological evaluation of some novel ?-aminobutyric acid aminotransferase (GABA-AT) inhibitors

In our present work, some novel substituted 4-phenyl-5-vinylpyrrolidin-2-one derivatives were designed, synthesized, and evaluated for their ?-aminobutyric acid-aminotransferase (GABA-AT) inhibition in-vivo anticonvulsant activity. Among all the synthesized derivatives, compound 7f was observed as most potent competitive inhibitor of GABA-AT (IC50 = 46.29 ± 3.19 µM, Ki 0.106 0.004 ?M). The activity against maximum electroshock (MES) PTZ, induced seizures test 7f, very significantly (P < 0.05) in comparison with standard Vigabatrin have shown an increase level GABA cortex region brain. ex-vivo studies also suggested reduced tissue necrosis. Finally, In-silico molecular docking dynamics that it forms desired amino acid residue interactions stable 50 ns active site pocket enzyme.