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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. 2018 Jan; 32(1)JB

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.

Authors+Show Affiliations

Department of Chemistry, Faculty of Science and Art, Bingol University, Bingol, 12000, Turkey.Vocational School of Health Services, Cumhuriyet University, Sivas, 58140, Turkey.Laboratory of Natural Product Research, Faculty of Health Sciences, Bingol University, Bingol, 12000, Turkey.Department of Chemistry, Faculty of Science and Art, Bingol University, Bingol, 12000, Turkey.Department of Chemistry, Faculty of Science and Art, Bingol University, Bingol, 12000, Turkey.Department of Chemistry, Faculty of Science, Ataturk University, Erzurum, 25240, Turkey.Department of Biometrics and Genetics, Faculty of Veterinary Medicine, Cumhuriyet University, Sivas, 58140, Turkey.Department of Chemistry, Faculty of Science, Ataturk University, Erzurum, 25240, Turkey.Department of Chemistry, Faculty of Science and Art, Bingol University, Bingol, 12000, Turkey.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

29131470

Citation

Bulut, Nilufer, et al. "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." Journal of Biochemical and Molecular Toxicology, vol. 32, no. 1, 2018.
Bulut N, Kocyigit UM, Gecibesler IH, et al. 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. 2018;32(1).
Bulut, N., Kocyigit, U. M., Gecibesler, I. H., Dastan, T., Karci, H., Taslimi, P., Durna Dastan, S., Gulcin, I., & Cetin, A. (2018). 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. Journal of Biochemical and Molecular Toxicology, 32(1). https://doi.org/10.1002/jbt.22006
Bulut N, et al. 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. 2018;32(1) PubMed PMID: 29131470.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Bulut,Nilufer, AU - Kocyigit,Umit M, AU - Gecibesler,Ibrahim H, AU - Dastan,Taner, AU - Karci,Huseyin, AU - Taslimi,Parham, AU - Durna Dastan,Sevgi, AU - Gulcin,Ilhami, AU - Cetin,Ahmet, Y1 - 2017/11/13/ PY - 2017/08/26/received PY - 2017/09/26/revised PY - 2017/10/13/accepted PY - 2017/11/14/pubmed PY - 2018/6/13/medline PY - 2017/11/14/entrez KW - 1,2,4-triazoles KW - antioxidant activity KW - carbonic anhydrase KW - enzyme inhibition KW - pyridine JF - Journal of biochemical and molecular toxicology JO - J. Biochem. Mol. Toxicol. VL - 32 IS - 1 N2 - 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. SN - 1099-0461 UR - https://www.unboundmedicine.com/medline/citation/29131470/Synthesis_of_some_novel_pyridine_compounds_containing_bis_124_triazole/thiosemicarbazide_moiety_and_investigation_of_their_antioxidant_properties_carbonic_anhydrase_and_acetylcholinesterase_enzymes_inhibition_profiles_ L2 - https://doi.org/10.1002/jbt.22006 DB - PRIME DP - Unbound Medicine ER -