Investigation of the toxicological and inhibitory effects of some benzimidazole agents on acetylcholinesterase and butyrylcholinesterase enzymes

WOS: 000470550600001PubMed: 31135232Benzimidazole, an anthelmintic used in the manufacture of human and veterinary drugs, is an important heterocyclic compound. In this work, I investigated the effect of drugs such as ricobendazole, thiabendazole, albendazole, and oxfendazole, on Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) enzyme activity. As kinetic studies, K-i and IC50 values were calculated separately for each drug, respectively. Study findings have shown that benzimidazoles inhibit both AChE and BChE enzymes at the nanomolar level. The compound that best was inhibited the AChE enzyme ricobendazole, and it was that the best inhibited the BChE enzyme thiabendazole. IC50 and K-i values were calculated 123.02 nM, 28.68 +/- 8.46 nM for AChE and 64.26 nM, 12.08 +/- 2.18 nM for BChE respectively. The types of inhibition indicated by the drugs were investigated and they were found to show non-competitive inhibition

The in vivo effects of cefazolin, cefuroxime, and cefoperazon on the carbonic anhydrase in different rat tissues

In this paper, the in vivo effects of some antibiotics including cefazolin, cefuroxime, and cefoperazon, on the activity of the carbonic anhydrase enzyme (CA) in heart, brain, eye, liver, and kidney tissues of rats were evaluated. For this purpose, 16 different groups, which each containing six rats (n = 6), were formed (control group, cefazolin groups, cefuroxime groups, and cefoperazon groups). The rats were necropsied 60 min after the intraperitoneal injection of the chemicals into the rats. The CA activities were measured for each tissue using esterase activity methods. The activity values for each tissue obtained were statistically calculated. The CA activities in the liver tissue were assessed, and the activities of the cefoperazon groups were decreased compared to the sham groups from the third hour (p<0.05). In the cefuroxime and cefoperazon groups, the CA activities in the eye tissue were decreased during the first 3 h and then increased (p<0.05)

In vitro and in silico enzyme inhibition effects of some metal ions and compounds on glutathione S-transferase enzyme purified from Vaccinium arctostapylous L.

Glutathione s-transferase (GST) is a class of enzymes that performs a wide array of biological functions. However, GST enzymes are most famously known for their roles in catalyzing the conjugation of reduced glutathione (GSH) to electrophilic centers on a wide variety of substrates to induce water-solubility to compounds as a protective antioxidant mechanism against toxic substances. In the present study, in vitro inhibition effects of coumarin, ascorbic acid, sodium sulfide, sodium azide, citric acid compounds, and Cd2+, Cu2+, Ni2+, Mg2+ metal ions against GST enzyme were determined. For this aim, the GST enzyme was purified from Vaccinium arctostapylous L. using the glutathione-agarose affinity chromatography and Sephadex G-100 gel filtration steps. The respective metals and chemical compounds were used at different concentrations for measuring their in vitro GST activity effects. The K-i values of these agents were determined as 0.450 +/- 0.13, 15.05 +/- 7.05, 0.009 +/- 0.001, 0.022 +/- 0.006, 0.120 +/- 0.36, 0.150 +/- 0.06, 0.223 +/- 0.03, 0.002 +/- 0.0003, and 0.136 +/- 0.06 mM, respectively. Finally, the molecular docking interactions of the compounds with the GST target enzyme were evaluated using Autodock Tools-1.5.6. The effective molecular interactions of coumarin, citric acid, ascorbic acid, and sodium sulfide with GST target enzyme were found with their binding lowest energy affinities -4.62, -3.04, -2.53, and -1.67 kcal/mol, respectively. Communicated by Ramaswamy H. Sarm

Synthesis, characterization, molecular docking, and biological activities of novel pyrazoline derivatives

In this study, synthesis of ethyl 2‐((4‐bromophenyl)diazenyl)‐3‐oxo‐phenylpropanoate 1 was carried out and a series of new 3H‐pyrazol‐3‐ones (P1–7) were synthesized from 1 as well as various hydrazines. The obtained yields of the synthesized compounds were moderate (40‒70%) and these compounds were confirmed by spectral data. These novel pyrazoline derivatives were effective inhibitor compounds of the human carbonic anhydrase I and II isozymes (hCAs I and II) and of the acetylcholinesterase (AChE) enzyme, with Ki values in the range of 17.4–40.7 nM for hCA I, 16.1–55.2 nM for hCA II, and 48.2–84.1 nM for AChE. In silico studies were performed on the compounds inhibiting hCA I, hCA II, and AChE receptors. On the basis of the findings, the inhibition profile of the new pyrazoline compounds at the receptors was determined

Investigation of spectroscopic, thermal, and biological properties of Fe-II, Co-II, Zn-II, and Ru-II complexes derived from azo dye ligand

In this study, the novel azo dye Fe-II , Co-II , Zn-II , and Ru-II complexes with an azo dye ligand (L: (E)-4-((4-methoxyphenyl)diazenyl)-3-methyl-1H-pyrazol-5-amine) were synthesized. The structures of the complexes were characterized by FT-IR, elemental analysis, UV-Vis, mass spectra (Fe-II and Co-II ), NMR spectra (only diamagnetic Zn-II and Ru-II ), thermogravimetric and differential thermal analysis (TA-DTA). All of the newly synthesized compounds were tested for their biochemical properties, including enzyme inhibitory and antioxidant activities. According to the in vitro ABTS, DPPH, CUPRAC, and FRAP antioxidant methods, the ligand and its metal complexes showed close antioxidant activities to the standards (BHA, BHT, ascorbic acid, and alpha-tocopherol). Enzyme inhibitions of the metal complexes were investigated against glutathione S-transferase (GST), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzymes. The best inhibition values (Ki) were observed for Ru(II) complex against GST (14.36 +/- 2.16 mu M), AChE (16.86 +/- 2.74 mu M), and BChE (14.12 +/- 2.04 mu M). (C) 2021 Elsevier B.V. All rights reserved

Synthesis and Characterization of Azo Dye Complexes as Potential Inhibitors of Acetylcholinesterase, Butyrylcholinesterase, and Glutathione S-Transferase

In this study, several metal(II) complexes (Fe, Co, Zn, and Ru) of an azo dye ligand (ADL) that, apart from pyrazole ring (PR), include anisole having (-OCH3) group at the m-substitue of the phenyl (L: (E)-4-((3-methoxyphenyl)diazenyl)-3-methyl-1H-pyrazol-5-amine) were prepared, characterized, and the biological activity studies were carried out. The structures of complexes were identified by elemental analysis, FTIR, UV-vis, mass spectra (Fe(II) and Co(II)), H-1-C-13 NMR spectra, and TGA-DTA. The azo ligand and its metal complexes were evaluated for their biological properties according to the enzyme inhibitory activities. The lowest K-i values of Co(II) complex against all three GST (19.48 +/- 2.17 mu M), AChE (22.14 +/- 3.74 mu M), and BChE (26.39 +/- 3.19 mu M) enzymes were verified as the most effective enzyme inhibition. The biological activity results suggest that the obtained complexes have good potentials to be used in further analyses to explore new pharmaceutical agents