Original Article In vitro brain GABA-transaminase activity of 1-(4- acetylphenyl)-3-aryloxypyrrolidine-2,5-dione derivatives Jigarkumar R. Patel a , Bharat Z. Dholakiya a, *, Nibha Mishra b a Department of Applied Chemistry, S. V. National Institute of Technology, Ichchanath, Surat 395007, Gujarat, India b Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi, India article info Article history: Received 13 March 2013 Accepted 10 April 2013 Available online 25 April 2013 Keywords: In vitro GABA-T activity Maleimide derivates Michael addition abstract Background: 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 objec- tive of obtaining lead compounds for future development as anticonvulsants. Methods: The inhibition by economically and efficiently synthesized targeted 1-(4-acetylphenyl)-3-aryloxypyrrolidine-2,5-diones 5aen with g-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. Results and discussion: 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 IC 50 (100.5  5.2 mM) and IC 50 (160.4  6.2 mM) respectively. This activity study was performed by using the fluorimetric analytical evaluation data compared with vigabatrin, a reference standard drug. Conclusion: 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. Copyright ª 2013, JPR Solutions; Published by Reed Elsevier India Pvt. Ltd. All rights reserved. 1. Introduction Epilepsy has been found to have point prevalence rates in the range of 4e10/1000 in the general population. 1 Despite this, anticonvulsant drugs are estimated to be useful in treating 90% of all epileptic patients. However, many antiepileptic drugs induce xenobiotic e metabolizing liver enzymes resulting in complex and undesirable side effects. Major medical breakthroughs in non-pharmacological therapies for the treatment of epilepsy in the near future seem remote, that is why, the search for new antiepileptic drugs with lower toxicity and fewer side effects continues. 2 g-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain, which controls the excitability of many central nervous * Corresponding author. Tel.: þ91 9428949595; fax: þ91 (0) 261 227334. E-mail address: bzd.svnit@gmail.com (B.Z. Dholakiya). Available online at www.sciencedirect.com journal homepage: www.elsevier.com/locate/jopr journal of pharmacy research 6 (2013) 442 e446 0974-6943/$ e see front matter Copyright ª 2013, JPR Solutions; Published by Reed Elsevier India Pvt. Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jopr.2013.04.012