Anticonvulsant Activity of 2-(Substituted-imino)thiazolidin-4-ones

Abstract

A novel series of 2-(substituted-imino)thiazolidin-4-ones were synthesized and evaluated for anticonvulsant activity using the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (Sc-PTZ) assays and their neurotoxicity was measured by the rotarod test. The results of these tests demonstrated that 2-(4-(pentyloxy)phenylimino)thiazolidin-4-one (5d) was the most potent anticonvulsant, with ED₅₀ value of 18.5 mg/kg and 15.3 mg/kg in the MES and Sc-PTZ tests, and protective index (PI=TD₅₀/ED₅₀) values of 10.6 and 12.8 respectively. 5d was much safer than a reference drug Carbamazepine.

Key words

thiazolidin-4-one - anticonvulsant - MES - Sc-PTZ - neurotoxicity

• References

• 1 Blume WT, Luder HO, Mizrahi E et al. Glossary of Descriptive Terminology for Ictal Semiology: Report of the ILAE Task Force on Classification and Terminology. Epilepsia 2001; 42: 1212-1218
• 2 Epilepsy Foundation. Statistics. 2004 Available at: http://www.epilepsyfoundation.org/answerplace/statistics.cfm Accessed January 26, 2005
• 3 Kwan P, Brodie MJ. Early Identification of Refractory Epilepsy. N Eng J Med 2000; 342: 314-319
• 4 Chen J, Sun XY, Chai KY et al. Synthesis and anticonvulsant evaluation of 4-(4-alkoxylphenyl)-3-ethyl-4H-1,2,4-triazoles as open-chain analogues of 7-alkoxyl-4,5-dihydro[1,2,4]triazolo[4,3-a]quinolines. Bioorg Med Chem 2007; 15: 6775-6781
• 5 Wei CX, Guan LP, Jia JH et al. Synthesis of 2-substituted-6-(4 H -1,2,4-triazol-4-yl)benzo[ d ]oxazoles as potential anticonvulsant agents. Arch Pharm Res 2009; 32: 23-31
• 6 Thenmozhiyal JC, Wong PT, Chui WK. Anticonvulsant Activity of Phenylmethylenehydantoins: A Structure-Activity Relationship Study. J Med Chem 2004; 47: 1527-1535
• 7 Wu S, Guo W, Teraishi F et al. Anticancer Activity of 5-Benzylidene-2-Phenylimino-1, 3-Thiazolidin- 4-one (BPT) Analogs. Med Chem 2006; 2: 597-605
• 8 Vicini P, Geronikaki A, Incerti M et al. 2-Heteroarylimino-5-benzylidene-4-thiazolidinones analogues of 2-thiazolylimino-5-benzylidene-4-thiazolidinones with antimicrobial activity: Synthesis and structure-activity relationship. Bioorg Med Chem 2008; 16: 3714-3724
• 9 Vicini P, Geronikaki A, Anastasia K et al. Synthesis and antimicrobial activity of novel 2-thiazolylimino-5-arylidene-4-thiazolidinones. Bioorg Med Chem 2006; 14: 3859-3864
• 10 Krall RJ, Penry JK, White BG et al. Pentylenetetrazole-Induced Changes in Zebrafish Behavior, Neural Activity, and c-fos Expression. Epilepsia 1978; 19: 409-428
• 11 Taranalli AD, Bhat AR, Srinivas S et al. Antiinflammatory, Analgesic and Antipyretic Activity of Certain Thiazolidinones. Indian J Pharm Sci 2008; 70: 159-164
• 12 Sadaf JG, Ozair A, Suroor AK et al. Synthesis of some derived thiazolidin-4-one, azetidin-2-one and 1,3,4-oxadiazole ring systems from Isoninicotinic acid hydrazide: A novel class of potential anticonvulsant agents. Der Pharmacia Lettre 2009; 1: 1-8
• 13 Washington (DC). Guide for the Care and Use of Laboratory Animals (Eighth edition), Committee for the Update of the Guide for the Care and Use of Laboratory Animals. National Research Council 2010
• 14 Hamilton MA, Russo RC, Thurston RC. Trimmed Spearman-Karber method for estimating median lethal concentration in toxicity bioassays. Env Sci Technol 1977; 7: 714-719
• 15 Liu XK, Cui X, Hong L et al. Synthesis of 2-(4-substituted-bmethylpiperazin-1-yl)-N-(3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazin-7-yl)aceta mides and their positive inotropic evaluation. Eur J Med Chem 2009; 44: 3027-3031
• 16 Radwan MA, Ragab EA, Sabry NM et al. Synthesis and biological evaluation of new 3-substituted indole derivatives as potential anti-inflammatory and analgesic agents. Bioorg Med Chem 2007; 15: 3832-3841
• 17 Ottanà R, Maccari R, Barreca ML et al. 5-Arylidene-2-imino-4-thiazolidinones: Design and synthesis of novel anti-inflammatory agents. Bioorg Med Chem 2005; 13: 4243-4252
• 18 Ottaná R, Mazzon E, Dugo L et al. Modeling and biological evaluation of 3,3′-(1,2-ethanediyl)bis[2-(4-methoxyphenyl)-thiazolidin-4-one], a new synthetic cyclooxygenase-2 inhibitor. Eur J Pharmacol 2002; 448: 71-80
• 19 Porter RJ, Cereghino JJ, Gladding GD et al. Antiepileptic Drug Development Program. Cleve Clin Q 1984; 51: 293-305
• 20 Sun XY, Jin YZ, Li FN et al. Synthesis of 8-alkoxy-4,5-dihydro-[1,2,4]triazole[4,3-a]quinoline-1-ones and evaluation of their anticonvulsant properties. Arch Pharm Res 2006; 29: 1080-1085