Synthesis of some novel pyridine compounds containing bis-1,2,4-triazole/thiosemicarbazide moiety and investigation of their antioxidant properties, carbonic anhydrase, and acetylcholinesterase enzymes inhibition profiles.
J Biochem Mol Toxicol
; 32(1)2018 Jan.
Article
em En
| MEDLINE
| ID: mdl-29131470
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 Ki s 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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piridinas
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Tiossemicarbazonas
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Triazóis
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Inibidores da Anidrase Carbônica
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Inibidores da Colinesterase
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Nootrópicos
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Antioxidantes
Idioma:
En
Revista:
J Biochem Mol Toxicol
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
TOXICOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Turquia