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

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-(pmethoxyphenyl)hydrazinecarbothioamide] (3c) showed very high activity with value of 72.93% against 1,1-diphenyl-2-picrylhydrazyl free radical at the concentration of 25 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.

Synthesis and characterization of novel substituted thiophene derivatives and discovery of their carbonic anhydrase and acetylcholinesterase inhibition effects

“…For the computation of K i values of these compounds, three diverse, novel substituted thiophene derivatives ( 1, 2a‐e, 3, and 4 ) concentrations were utilized. One AChE enzyme unit is the amount of enzyme that hydrolyzes 1.0 mol of AChI to choline and acetate per minute at pH 8.0 at 37°C . Finally, the Lineweaver‐Burk curves were drawn.…”

The effects of hesperidin on sodium arsenite-induced different organ toxicity in rats on metabolic enzymes as antidiabetic and anticholinergics potentials: A biochemical approach

“…Additionally, the defined key role of CA inhibitor (CAI) molecules as antiglaucoma compounds and diuretics factor, it has recently appointed which they have capability as anticonvulsant, antiobesity, antiinfective, and anticancer drugs (Gulçin et al, ; Koçyiğit, Taşkıran, et al, ; Taslimi, Osmanova, et al, ; Taslimi, Caglayan, et al, ; Yamali, Gül, Ece, Taslimi, & Gulçin, ). Indeed, there are diverse approved compounds as AChEIs like galanthamine, donepezil, tacrine molecule, and rivastigmine for the treatment of AD (Bulut et al, ). Conforming to the cholinergic hypothesis, impairment of the cholinergic pathways plays a major role in the development of neurodegenerative diseases like depression, schizophrenia, AD problems with the regulation of traumatic brain injury and sleep (Huseynova et al, ; Taslimi, Sujayev, et al, ).…”

Inhibition profiles of Voriconazole against acetylcholinesterase, α‐glycosidase, and human carbonic anhydrase I and II isoenzymes

“…In the CA isoenzyme section, changes in absorbance were measured for 3 minutes at 348 nm. p ‐Nitrophenylacetate (PNA) was utilized as a substrate that was converted by both isoenzymes to the p ‐nitrophenolate according to the Verpoorte method, as described previously …”