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Anticonvulsant and Neurotoxicity Evaluation of Some Novel Kojic Acids and Allomaltol Derivatives
Author(s) -
Aytemir Mutlu Dilsiz,
Çalış Ünsal
Publication year - 2010
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200900236
Subject(s) - kojic acid , chemistry , hydroxymethyl , pyran , anticonvulsant , neurotoxicity , stereochemistry , toxicity , organic chemistry , epilepsy , medicine , enzyme , tyrosinase , psychiatry
A series of new 3‐hydroxy‐6‐hydroxymethyl/methyl‐2‐substituted 4 H ‐pyran‐4‐ones were synthesized and prepared by the reaction of kojic acid or allomaltol with piperidine derivatives and formaline as potential anticonvulsant compounds. The structure of the synthesized compounds was confirmed using the elemental analysis results and the spectroscopic techniques such as IR, 1 H‐NMR, and ESI‐MS. Anticonvulsant activities 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 in accordance with the procedures of the Antiepileptic Drug Development (ADD) program. According to the activity studies and at all doses, 3‐hydroxy‐2‐[(4‐hydroxy‐4‐phenylpiperidin‐1‐yl)methyl]‐6‐methyl‐4 H ‐pyran‐4‐one (compound 1 ), 2‐{[4‐(4‐chlorophenyl)‐3,6‐dihydropyridin‐1(2 H )‐yl]methyl}‐3‐hydroxy‐6‐methyl‐4 H ‐pyran‐4‐one (compound 6 ), 2‐[(4‐acetyl‐4‐phenylpiperidin‐1‐yl)methyl]‐3‐hydroxy‐6‐(hydroxymethyl)‐4 H ‐pyran‐4‐one (compound 11 ), and 2‐{[4‐(4‐chlorophenyl)‐3,6‐dihydropyridin‐1(2 H )‐yl] methyl}‐3‐hydroxy‐6‐hydroxymethyl‐4 H ‐pyran‐4‐one (compound 12 ) were found to have anticonvulsant activity against MES‐induced seizures at 4 h. Also, 2‐{[4‐(4‐bromophenyl)‐4‐hydroxypiperidin‐1‐yl]methyl}‐3‐hydroxy‐6‐(hydroxymethyl)‐4 H ‐pyran‐4‐one (compound 8 ) was determined to be the most active compound against scMet‐induced seizures at all doses at 0.5 and 4 h. In the rotorod neurotoxicity screening, all compounds showed no toxicity at all doses.