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

被引:81
作者
Bulut, Nilufer [1 ]
Kocyigit, Umit M. [2 ]
Gecibesler, Ibrahim H. [3 ]
Dastan, Taner [1 ]
Karci, Huseyin [1 ]
Taslimi, Parham [4 ]
Dastan, Sevgi Durna [5 ]
Gulcin, Ilhami [4 ]
Cetin, Ahmet [1 ]
机构
[1] Bingol Univ, Fac Sci & Art, Dept Chem, TR-12000 Bingol, Turkey
[2] Cumhuriyet Univ, Vocat Sch Hlth Serv, TR-58140 Sivas, Turkey
[3] Bingol Univ, Lab Nat Prod Res, Fac Hlth Sci, TR-12000 Bingol, Turkey
[4] Ataturk Univ, Dept Chem, Fac Sci, TR-25240 Erzurum, Turkey
[5] Cumhuriyet Univ, Dept Biometr & Genet, Fac Vet Med, TR-58140 Sivas, Turkey
关键词
1,2,4-triazoles; antioxidant activity; carbonic anhydrase; enzyme inhibition; pyridine; II INHIBITION; ISOENZYMES I; BUTYRYLCHOLINESTERASE; DERIVATIVES; ESTERASE; BROMOPHENOLS; SULFONAMIDES; HETEROCYCLES; BIOACTIVITY; ALZHEIMERS;
D O I
10.1002/jbt.22006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 mu g/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 K(i)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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页数:10
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