In vitro brain GABA-transaminase activity of 1-(4-acetylphenyl)-3-aryloxypyrrolidine-2,5-dione derivatives

• Published in: Journal of pharmacy research 2013-04, Vol.6 (4), p.442-446
• Main Authors: Patel, Jigarkumar R., Dholakiya, Bharat Z., Mishra, Nibha
• Format: Article
• Language: English
• Subjects: In vitro GABA-T activity; Maleimide derivates; Michael addition
• ISSN: 0974-6943; 0974-6943
• DOI: 10.1016/j.jopr.2013.04.012

Preparation of a new series of Michael adducts as an 1-(4-acetylphenyl)-3-aryloxypyrrolidine-2,5-dione derivates using cellulose sulfuric acid catalyst with objective of obtaining lead compounds for future development as anticonvulsants. The inhibition by economically and efficiently synthesized targeted 1-(4-acetylphenyl)-3-aryloxypyrrolidine-2,5-diones 5a–n with γ-aminobutyric acid (GABA)-transaminase activity was studied with homogenized mice brain as described by Fowler & Qume followed by the fluorimetric analysis using Salvador & Albers method. All the compounds were characterized by physical, spectroscopic and elemental analysis. Among the fourteen Michael adducts of 1-(4-acetylphenyl)-pyrrole-2,5-dione, 1-(4-acetylphenyl)-3-(4-Bromophenyloxy)-pyrrolidine-2,5-dione 5d and 1-(4-acetylphenyl)-3-(Salicyldehydoxy)-pyrrolidine-2,5-dione 5h showed more potent as in vitro barain GABA-transaminase activity with IC50 (100.5 ± 5.2 μM) and IC50 (160.4 ± 6.2 μM) respectively. This activity study was performed by using the fluorimetric analytical evaluation data compared with vigabatrin, a reference standard drug. In conclusion, 1-(4-acetylphenyl)-3-(4-Bromophenyloxy)-pyrrolidine-2,5-dione 5d and 1-(4-acetylphenyl)-3-(Salicyldehydoxy)-pyrrolidine-2,5-dione 5h strongly fulfill where as 1-(4-acetylphenyl)-3-(2,4,6-Nitrophenyloxy)-pyrrolidine-2,5-dione 5l and 1-(4-acetylphenyl)-3-(2-Napthyloxy)-pyrrolidine-2,5-dione 5b significantly fulfill the criteria for mice brain GABA-T inhibitory agents.