Nilufer Bulut, U. M. Kocyigit, I. Gecibesler
Jan 1, 2018
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Influential Citations
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Journal
Journal of Biochemical and Molecular Toxicology
Abstract
Some novel derivatives of thiosemicarbazide and 1,2,4‐triazole‐3‐thiol were synthesized and evaluated for their biological activities. The title compounds were prepared starting from readily available pyridine‐2,5‐dicarboxylic acid. The reaction carboxylic acid with absolute ethanol afforded the corresponding dimethyl pyridine‐2,5‐dicarboxylate (1). The reaction of dimethyl‐2,5‐pyridinedicarboxylate (1) with hydrazine hydrate good yielded pyridine‐2,5‐dicarbohydrazide (2). Refluxing compound 2 with alkyl/aryl isothiocyanate derivatives for 3–8 h afforded 1,4‐disubstituted thiosemicarbazides (3a–e). Base‐catalyzed intra‐molecular dehydrative cyclization of these intermediates furnished the 4,5‐disubstituted bis‐mercaptotriazoles (4a–e) in good yield (85%–95%). Among the target compounds, 2,2′‐(pyridine‐2,5‐diyldicarbonyl)bis[N‐(p‐methoxyphenyl)hydrazinecarbothioamide] (3c) showed very high activity with value of 72.93% against 1,1‐diphenyl‐2‐picrylhydrazyl free radical at the concentration of 25 μg/mL. The inhibitory effects of the target compounds against acetylcholinesterase (AChE), hCA I, and II were studied. AChE, cytosolic hCA I and II isoforms were potently inhibited by synthesized these derivatives with Kis in the range of 3.07 ± 0.76–87.26 ± 29.25 nM against AChE, in the range of 1.47 ± 0.37–10.06 ± 2.96 nM against hCA I, and in the range of 3.55 ± 0.57–7.66 ± 2.06 nM against hCA II, respectively.