Carbamates Dotaz Zobrazit nápovědu
IARC monographs on the evaluation of carcinogenic risk of chemicals to man ; Vol. 12
282 s. : tab.
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- onkologie
- chemie, klinická chemie
Kinetics and mechanism of in vitro hydrolyses of acetylcholine and acetylthiocholine by carbamates were studied in a batch reactor at 25 degrees C, pH 8, and ionic strength of 0.11 M. Every hydrolysis was monitored by 3-4 independent methods. All studied hydrolyses can be described by the model of competitive inhibition with an irreversible step (k3). A table of obtained average values of rate constants and discussion of the resultes are given.
Series of twenty-five benzyl (2S)-2-(arylcarbamoyl)pyrrolidine-1-carboxylates was prepared and completely characterized. All the compounds were tested for their in vitro ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and the selectivity of compounds to individual cholinesterases was determined. Screening of the cytotoxicity of all the compounds was performed using a human monocytic leukaemia THP-1 cell line, and the compounds demonstrated insignificant toxicity. All the compounds showed rather moderate inhibitory effect against AChE; benzyl (2S)-2-[(2-chlorophenyl)carbamoyl]pyrrolidine-1-carboxylate (IC50 = 46.35 μM) was the most potent agent. On the other hand, benzyl (2S)-2-[(4-bromophenyl)-] and benzyl (2S)-2-[(2-bromophenyl)carbamoyl]pyrrolidine-1-carboxylates expressed anti-BChE activity (IC50 = 28.21 and 27.38 μM, respectively) comparable with that of rivastigmine. The ortho-brominated compound as well as benzyl (2S)-2-[(2-hydroxyphenyl)carbamoyl]pyrrolidine-1-carboxylate demonstrated greater selectivity to BChE. The in silico characterization of the structure-inhibitory potency for the set of proline-based carbamates considering electronic, steric and lipophilic properties was provided using comparative molecular surface analysis (CoMSA) and principal component analysis (PCA). Moreover, the systematic space inspection with splitting data into the training/test subset was performed to monitor the statistical estimators performance in the effort to map the probability-guided pharmacophore pattern. The comprehensive screening of the AChE/BChE profile revealed potentially relevant structural and physicochemical features that might be essential for mapping of the carbamates inhibition efficiency indicating qualitative variations exerted on the reaction site by the substituent in the 3'-/4'-position of the phenyl ring. In addition, the investigation was completed by a molecular docking study of recombinant human AChE.
- MeSH
- acetylcholinesterasa chemie MeSH
- butyrylcholinesterasa chemie MeSH
- cholinesterasové inhibitory chemická syntéza chemie farmakologie MeSH
- karbamáty chemická syntéza chemie farmakologie MeSH
- katalytická doména MeSH
- molekulární konformace MeSH
- prolin * chemie MeSH
- simulace molekulového dockingu MeSH
- vazba proteinů MeSH
- vazebná místa MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
In the literature, carbamates pesticides (CMs) have been implicated in the increasing prevalence of diseases associated with alterations of the immune response, such as hypersensitivity reactions, some autoimmune diseases and cancers. CMs may initiate, facilitate or exacerbate pathological immune processes, resulting in immunotoxicity by induction of mutations in genes coding for immunoregulatory factors and modifying immune tolerance. In the present study, oxidative stress and inhibition of esterases activities have been introduced as the main mechanisms of CMs induced immune dysregulation. In addition, the evidence on the relationship between CMs pesticide exposure, dysregulation of the immune system and predisposition to different types of cancers are criticized.
- MeSH
- cholinesterasové inhibitory farmakologie toxicita MeSH
- endokrinní disruptory MeSH
- imunitní systém * účinky léků MeSH
- insekticidy metabolismus toxicita MeSH
- karbamáty * metabolismus toxicita MeSH
- karcinogeneze chemicky indukované MeSH
- lidé MeSH
- nádory chemicky indukované MeSH
- oxidační stres MeSH
- pesticidy * metabolismus toxicita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Illegal poisoning of wildlife and domestic animals is a worldwide issue. The carbamates primarily used as pesticides are often misused for such a purpose. In this study, 181 birds, mammals and baits were analysed over the period 2004-2009 for possible intoxication by carbamates. Intoxication by carbamate carbofuran was diagnosed in 89 cases, and in another 19 cases (nine Wild Boars and 10 Bisons) intoxication with another carbamate-methomyl - was proven. Incidental ingestion of the marten bait was the main cause of intoxication. Although the distribution of carbofuran was prohibited in 2007, no decline in the number of intoxicated animals in the following two years was detected. New cases of intoxication by carbofuran are anticipated in the future until all remaining stock is expended.
- MeSH
- acetylcholinesterasa analýza MeSH
- cholinesterasové inhibitory otrava škodlivé účinky toxicita MeSH
- chromatografie plynová MeSH
- financování organizované MeSH
- gastrointestinální obsah chemie MeSH
- histologické techniky MeSH
- játra chemie MeSH
- karbamáty otrava MeSH
- karbofuran otrava MeSH
- methomyl otrava MeSH
- organofosforové sloučeniny toxicita MeSH
- otrava organofosfáty MeSH
- otrava epidemiologie veterinární MeSH
- pesticidy otrava toxicita MeSH
- příčina smrti MeSH
- ptáci MeSH
- retrospektivní studie MeSH
- rezidua pesticidů analýza MeSH
- savci MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
