Synthesis and anticonvulsant activity of new kojic acid derivatives.
A series of new 3-hydroxy-6-hydroxymethyl-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-chlorophenyl)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.
Aytemir
Mutlu Dilsiz
MD
Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Ankara, Turkey. mutlud@hacettepe.edu.tr
Septioğlu
Ebubekir
E
Caliş
Unsal
U
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D003292:Convulsants; D004597:Electroshock; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008352:Mannich Bases; D051379:Mice; D020258:Neurotoxicity Syndromes / Q000523:psychology; D010433:Pentylenetetrazole; D004856:Postural Balance / Q000187:drug effects; D011753:Pyrones / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D003292:Convulsants; D007202:Indicators and Reagents; D008352:Mannich Bases; D011753:Pyrones; C011890:kojic acid; D010433:Pentylenetetrazole