Arzneimittelforschung, Table of Contents Arzneimittelforschung 2010; 60(1): 22-29DOI: 10.1055/s-0031-1296244 CNS-active Drugs · Hypnotics · Psychotropics · Sedatives Editio Cantor Verlag Aulendorf (Germany)Synthesis and anticonvulsant activity of new kojic acid derivatives Authors Author Affiliations Mutlu Dilsiz Aytemir 1 Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Ankara, Turkey Ebubekir Septioğlu 1 Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Ankara, Turkey Ünsal Çaliş 1 Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Ankara, Turkey Recommend Article Abstract Buy Article(opens in new window) Abstract A series of new 3-hydroxy-6-hydroxy-methyl-2-substituted 4H-pyran-4-one derivatives were synthesized as potential anticonvulsant compounds. Mannich compounds were prepared by the reaction of appropriate substituted piperazine derivatives with kojic acid and formaline. The structure of the synthesized compounds was confirmed using the elementary analysis results and spectroscopic techniques such as IR, 1H-NMR and ESI-MS. Anticonvulsant activities of the synthesized compounds were examined by maximal electroshock (MES) and subcutaneous Metrazol (scMet) induced seizure tests. Neurotoxicity was determined by the rotorod toxicity test. All these tests were performed according to procedures of the Antiepileptic Drug Development (ADD) program. According to the activity studies, 2-[4-(4-chlorophe-nyl) piperazin-1-ylmethyl]-3-hydroxy-6-hydroxymethyl-4H-pyran-4-one (compound 11) against MES seizures and 3-hydroxy-6-hydroxymethyl-2-[4-(2-methoxyphenyl)piperazin-1-ylmethyl]-4H-pyran-4-one (compound 7) against scMet seizures were determined to be the most active compounds at all doses without neurotoxicity Key words Key wordsKojic acid derivatives, anticonvulsant activity, neurotoxicity - Mannich reaction Full Text References References 1 Burdock GA, Soni M, Carabin IG. Evaluation of health aspects of kojic acid in food. Regul Toxicol and Pharm. 2001; 33: 80-101 2 Brtko J, Rondahl L, Fickova M, Hudecova D, Eybl V, Uher M. Kojic acid and its derivatives: History and present state of art. Cent Eur J Publ Health. 2004; 12: 16-8 3 Bentley R. From miso, saké and shoyu to cosmetics: a century of science for kojic acid. Nat Prod Rep. 2006; 23: 1046-62 4 Beelik A, Purves CB. Some new reactions and derivatives of kojic acid. 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