Synthesis and anticonvulsant activity of new kojic acid derivatives

Abstract

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.

Synthesis and biological activities of new Mannich bases of chlorokojic acid derivatives

“…The methylene group protons of 1-11 appeared as singlet peaks at 3.51-3.72 ppm. The ESI mass spectra of all compounds showed suitable peaks in accordance with previously study (Aytemir et al, 2010 The antibacterial and antifungal activity profiles of the newly synthesized compounds were assessed for antimicrobial activity against both standards and the isolated strains of microorganism. Tables 2 and 3 describe the in vitro antimicrobial activity with the MIC values of compounds 1-11.…”

“…According to its antibacterial and fungicidal properties, kojic acid is used as a food additive to prevent browning (Burdock et al, 2001;Brtko et al, 2004;Bentley, 2006). Moreover, kojic acid derivatives exhibit a number of interesting bioactivities including herbicidal (Veverka and Kralovicova, 1990), anti-speck (Uchino et al, 1988), pesticide and insecticide (Alverson, 2003), antitumor activity (Higa et al, 2007), anti-diabetic (Xiong and Pirrung, 2008), antiepileptic (Aytemir et al, 2004(Aytemir et al, , 2010, modest anti-inflammatory effect (Brtko et al, 2004), and as a skin-whitening product in cosmetic (Burdock et al, 2001;Bentley, 2006).…”

Anticonvulsant and Neurotoxicity Evaluation of Some Novel Kojic Acids and Allomaltol Derivatives

“…When the effects of different piperazine rings upon the activity were examined, kojic acid derivatives were found to be more active than allomaltol derivatives [6,9]. Whenever mono-substituted piperidine derivatives or morpholine rings (They were also used instead of the piperazine ring) were used, the anticonvulsant activity of these Mannich bases of allomaltol derivatives decreased [7,8].…”

MCM-41-SO3H: an efficient, reusable, heterogeneous catalyst for the one-pot, three-component synthesis of pyrano[3,2-b]pyrans

“…Kojic acid derivatives possess wide-ranging pharmacological activities such as antifungal [4], anti-neoplastic [5], antiproliferative [6], anti-HIV [7], anticonvulsant [8], anti-inflammatory [9], antioxidative [10], antibacterial [11], and tyrosinase inhibitory activities [12]. Because of these valuable properties, kojic acid derivatives are of great interest for the pharmaceutical chemistry.…”