Synthesis, molecular docking and biological evaluation of N,N-disubstituted 2-aminothiazolines as a new class of butyrylcholinesterase and carboxylesterase inhibitors

Махаева, Галина Ф.; Boltneva, Natalia P.; Lushchekina, Sofya V.; Serebryakova, Olga G.; Stupina, Tatyana S.; Terentiev, Alexei A.; Серков, И. В.; Прошин, А. Н.; Бачурин, С. О.; Richardson, Rudy J.

doi:10.1016/j.bmc.2016.01.031

Cited by 59 publications

(22 citation statements)

References 48 publications

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“…AChE and BChE activities were determined by the colorimetric Ellman method (λ 412 nm) [15], with some minor modifications as described in detail in [16], using ATCh (1 mM) as substrate. The assay solution consisted of 0.1 M K/Na phosphate buffer pH 7.5, 25 • C, 0.33 mM DTNB, 0.02 unit/mL AChE or BChE.…”

Section: Esterase Inhibition Assaymentioning

confidence: 99%

Arachidonoylcholine and Other Unsaturated Long-Chain Acylcholines Are Endogenous Modulators of the Acetylcholine Signaling System

et al. 2020

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Cholines acylated with unsaturated fatty acids are a recently discovered family of endogenous lipids. However, the data on the biological activity of acylcholines remain very limited. We hypothesized that acylcholines containing residues of arachidonic (AA-CHOL), oleic (Ol-CHOL), linoleic (Ln-CHOL), and docosahexaenoic (DHA-CHOL) acids act as modulators of the acetylcholine signaling system. In the radioligand binding assay, acylcholines showed inhibition in the micromolar range of both α7 neuronal nAChR overexpressed in GH4C1 cells and muscle type nAChR from Torpedo californica, as well as Lymnaea stagnalis acetylcholine binding protein. Functional response was checked in two cell lines endogenously expressing α7 nAChR. In SH-SY5Y cells, these compounds did not induce Ca2+ rise, but inhibited the acetylcholine-evoked Ca2+ rise with IC50 9 to 12 μM. In the A549 lung cancer cells, where α7 nAChR activation stimulates proliferation, Ol-CHOL, Ln-CHOL, and AA-CHOL dose-dependently decreased cell viability by up to 45%. AA-CHOL inhibited human erythrocyte acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BChE) by a mixed type mechanism with Ki = 16.7 ± 1.5 μM and αKi = 51.4 ± 4.1 μM for AChE and Ki = 70.5 ± 6.3 μM and αKi = 214 ± 17 μM for BChE, being a weak substrate of the last enzyme only, agrees with molecular docking results. Thus, long-chain unsaturated acylcholines could be viewed as endogenous modulators of the acetylcholine signaling system.

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Section: Esterase Inhibition Assaymentioning

confidence: 99%

Arachidonoylcholine and Other Unsaturated Long-Chain Acylcholines Are Endogenous Modulators of the Acetylcholine Signaling System

et al. 2020

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“…However, during the progression of AD, brain AChE levels decline while BChE activity increases, suggesting that ACh hydrolysis may occur to a greater extent via BChE catalysis. In this regard, it has been reported that highly selective inhibition of BChE is important in raising ACh levels and improving cognition 103 . The inhibition effects of novel tetrahydropyrimidine-5-carboxylates (1-3) against AChE/BChE activities were measured according to spectrophotometric method described by Ellman et al 84 Acetylthiocholine iodide/butyrylthiocholine iodide (AChI/BChI) was used as substrates for the reactions.…”

Section: Biochemical Resultsmentioning

confidence: 99%

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

Sujayev

Garibov

Taslimi

et al. 2016

Journal of Enzyme Inhibition and Medicinal Chemistry

107

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2-(Methacryloyloxy)ethyl 6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate, is a cyclic urea derivative synthesized from urea, 2-(methacryloyloxy) ethyl acetoacetate and substituted benzaldehyde, and tested in terms of the inhibition of two physiologically relevant carbonic anhydrase (CA) isozymes I and II. Acetylcholinesterase (AChE) is found in high concentrations in the red blood cells and brain. Butyrylcholinesterase (BChE) is another enzyme abundantly present in the liver and released into blood in a soluble form. Also, they were tested for the inhibition of

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“…12 In this context, thiazolines are a class of ligands formed by heterocyclic five-membered rings that contain nitrogen and sulfur atoms, which have a plurality of coordination modes. 13 Thiazolines are known for various biological activities such as anti-inflammatory, 14 anticancer 15 and antimicrobial, 16 which make the thiazoline-derived compounds important in medicinal chemistry studies. Therefore, compounds derived from 2-thiazolidine-2-thiol have been synthesized and used in metal complexes formation [16][17][18] such as the 2-thiazoline-2-thiol-derivative ligand 19 that is included in a class of ligands called scorpionates.…”

Section: Introductionmentioning

confidence: 99%

SYNTHESIS, CHARACTERIZATION AND ANTIMICROBIAL ACTIVITY OF NEW Cu (II), Co (II) AND Sn (II) COMPLEXES WITH THE SODIUM HYDROTRIS(2-MERCAPTOTHIAZOLYL)BORATE LIGAND

Ferreira¹,

Andrade²,

Lima³

et al. 2020

Quim. Nova

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Recebido em 27/11/2019; aceito em 05/02/2020; publicado na web em 16/04/2020 The emergence of antibiotic resistance among microbial pathogens is a serious public health problem, resulting in a constant need of discovering new antibiotics. For this purpose, we synthetized and determined the antimicrobial activity of copper (Cu), cobalt (Co), and tin (Sn) complexes coordinated with scorpionate ligand in a tridentate mode against microorganisms of clinical importance. New complexes with the sodium hydrotris(2-mercaptothiazolyl)borate ligand were characterized by physicochemical and spectroscopic techniques (UV-vis, IR, 1 H and 13 C NMR). Moreover, their antimicrobial activity was evaluated using microdilution broth method. Cytotoxicity was determined in Vero cells and the selectivity index (SI) was calculated. The coordination with metals increased the ligand antimicrobial activity, which showed no activity when evaluated alone (MIC>1,080 µM). Cu-complex (1) had activity against Candida albicans and C. krusei, with MICs of 130 and 66 µM, respectively. The compounds had low toxicity on Vero cells and chemo-informatics assays corroborated a low systemic toxic effect. The SI revealed that the compound 1 was 16 times more selective for C. krusei and 8 times more selective for C. albicans in relation to Vero cells. The Cu-complex stands out as a potential prototype for the development of new antifungal agents.

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Synthesis, molecular docking and biological evaluation of N,N-disubstituted 2-aminothiazolines as a new class of butyrylcholinesterase and carboxylesterase inhibitors

Cited by 59 publications

References 48 publications

Arachidonoylcholine and Other Unsaturated Long-Chain Acylcholines Are Endogenous Modulators of the Acetylcholine Signaling System

Arachidonoylcholine and Other Unsaturated Long-Chain Acylcholines Are Endogenous Modulators of the Acetylcholine Signaling System

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

SYNTHESIS, CHARACTERIZATION AND ANTIMICROBIAL ACTIVITY OF NEW Cu (II), Co (II) AND Sn (II) COMPLEXES WITH THE SODIUM HYDROTRIS(2-MERCAPTOTHIAZOLYL)BORATE LIGAND

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