Synthesis of some tetrahydropyrimidine-5-carboxylates, determination of their metal chelating effects and inhibition profiles against acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase

J Biochem & Molecular Tox

Osmanova

Çağlayan

et al. 2018

Self Cite

The thiolation reaction was carried out in a benzene solution at 80°C and p-substituted ketones and mercaptoacetic acid in a molar ratio (1:4) of in the presence of a catalytic amount of toluene sulfonic acids. The enzyme inhibition activities of the novel amides of 1,1-bis-(carboxymethylthio)-1-arylethanes derivatives were investigated. These novel amides of 1,1-bis-(carboxymethylthio)-1-arylethanes derivatives showed good inhibitory action against acetylcholinesterase (AChE) butyrylcholinesterase (BChE), and human carbonic anhydrase I and II isoforms (hCA I and II). AChE inhibitors, interacting with the enzyme as their primary target, are applied as relevant drugs and toxins. Many clinically established drugs are carbonic anhydrase inhibitors, and it is highly anticipated that many more will eventually find their way into the market. The novel synthesized compounds inhibited AChE and BChE with K values in the range of 0.64-1.47 nM and 9.11-48.12 nM, respectively. On the other hand, hCA I and II were effectively inhibited by these compounds, with K values between 63.27-132.34 and of 29.63-127.31 nM, respectively.

Section: Introductionmentioning

confidence: 99%

Novel amides of 1,1‐bis‐(carboxymethylthio)‐1‐arylethanes: Synthesis, characterization, acetylcholinesterase, butyrylcholinesterase, and carbonic anhydrase inhibitory properties

J Biochem & Molecular Tox

Osmanova

Çağlayan

et al. 2018

Self Cite

“…The proteins present in the column eluates were spectrophotometrically (UV‐VIS spectrophotometer, UVmini‐1240; Shimadzu, Kyoto, Japan) recorded at 280 nm . For investigating the inhibition result of each isoform, some novel amide and thiazolidine‐4‐ones derivatives were used and an activity (%)[amides and thiazolidine‐4‐ones] graph was drawn . Additionally, for determining K i values, three various novel amides, and thiazolidine‐4‐ones, concentrations were tested .…”

Section: Methodsmentioning

confidence: 99%

“…hCA II has an important role in bicarbonate (HCO 3 − ) production in the eye, and it hence has a validated purpose for the treatment of glaucoma . hCA I is defined by an orphan purpose, the presence of extracellular CA I in the blood–brain barrier or blood–retinal barrier can compel vasogenic edema

C {normalO}_{2} + {normalH}_{2} normalO \overset{CA}{\Leftrightarrow} {normalH}_{2} C {normalO}_{3} \Leftrightarrow {HCO}_{3}^{-} + H^{+}

…”

Section: Introductionmentioning

confidence: 99%

Discovery of potent carbonic anhydrase, acetylcholinesterase, and butyrylcholinesterase enzymes inhibitors: The new amides and thiazolidine-4-ones synthesized on an acetophenone base

Osmanova

Gülçın

et al. 2017

J Biochem Mol Toxicol

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Compounds containing nitrogen and sulfur atoms can be widely used in various fields, including industry, medicine, biotechnology, and chemical technology. Among them, amides of acids and heterocyclic compounds have an important place. These amides and thiazolidine-4-ones showed good inhibitory action against butyrylcholinesterase (BChE), acetylcholinesterase (AChE), and human carbonic anhydrase isoforms. AChE exists at high concentrations in the brain and red blood cells. BChE is an important enzyme that is plentiful in the liver, and it is released into the blood in a soluble form. They were demonstrated to have effective inhibition profiles with K values of 23.76-102.75 nM against hCA I, 58.92-136.64 nM against hCA II, 1.40-12.86 nM against AChE, and 9.82-52.77 nM against BChE. On the other hand, acetazolamide showed K value of 482.63 ± 56.20 nM against hCA I, and 1019.60 ± 163.70 nM against hCA II. Additionally, Tacrine inhibited AChE and BChE, showing K values of 397.03 ± 31.66 and 210.21 ± 15.98 nM, respectively.

“…However, it depends on the reaction conditions, such as metal ion, its concentration, the pH of the medium, and the nature of the hydrazide ligand. [16,17] Alzheimer's disease (AD) is associated with perturbation of the cholinergic device, which affects attention functioning and memory. [13][14][15] Human CAs (hCAs) presently recorded belong to the -CA family, and create drug purposes for obtaining antiglaucoma agents, diuretics, antiobesity, antitumor drugs, and antiepileptics.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, crystal structure and biological evaluation of spectroscopic characterization of Ni(II) and Co(II) complexes with N‐salicyloil‐N′‐maleoil‐hydrazine as anticholinergic and antidiabetic agents

Gondolova

J Biochem & Molecular Tox

Medjidov

et al. 2018

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[Ni(C H N O ) (H O) ]•3(C H NO) (1) and [Co(C H N O ) (H O) ]•3(C H NO) (2) are synthesized and characterized by elemental analysis, FT-IR spectra, magnetic susceptibility, and thermal analysis. In addition, the crystal structure of Ni(II) complex is presented. Both complexes show distorted octahedral geometry. In 1 and 2, metal ions are coordinated by two oxygen atoms of salicylic residue and two nitrogen atoms of maleic amide residue from two ligands, and two oxygen atoms from two water molecules. In this paper, both compounds showed excellent inhibitory effects against human carbonic anhydrase (hCA) isoforms I, and II, α-glycosidase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE). Compounds 1 and 2 had Ki values of 18.36 ± 4.38 and 26.61 ± 7.54 nM against hCA I and 13.81 ± 3.02 and 29.56 ± 6.52 nM against hCA II, respectively. On the other hand, their Ki values were found to be 487.45 ± 54.18 and 453.81 ± 118.61 nM against AChE and 199.21 ± 50.35 and 409.41 ± 6.86 nM against BChE, respectively.