Abstract
Two series A and B of 12 and 7 new carbamate derivates were tested in vitro as acetylcholinesterase inhibitors. The tests were performed in the batch stirred reactor at 25°C, pH 8, ionic strength 0.11 M and catalytic activity of the enzyme preparation 0.14 U mL-1 of the reaction mixture. The temporal dependences of actual concentrations of acetylcholine, choline and acetic acid were determined by two independent analytical methods, HPLC and pH-stat. For all used inhibitors, the model of competitive irreversible inhibition was valid. The inhibition rate constant k3 and qualified estimation of the absolute acetylcholinesterase concentration in the reaction mixture were calculated. The partition coefficients Kow between n-octanol and water of all used inhibitors were determined. The k3 and Kow values were correlated with the Hammett and Hansch substituent constants and with the calculated docking and binding energies of the reaction between the tested inhibitors and acetylcholinesterase.
Keywords: Acetylcholine, hydrolysis, enzymatic, in vitro, acetylcholinesterase, carbamates, inhibition, kinetics, HPLC, docking energies
Current Enzyme Inhibition
Title:Kinetics of In Vitro Inhibition of Acetylcholinesterase by Nineteen New Carbamates
Volume: 7 Issue: 4
Author(s): Marketa Kovarova, Mahmud T.H. Khan, Karel Komers, Patrik ParÃk, Alexander Cegan, Martina Zatloukalova
Affiliation:
Keywords: Acetylcholine, hydrolysis, enzymatic, in vitro, acetylcholinesterase, carbamates, inhibition, kinetics, HPLC, docking energies
Abstract:
Two series A and B of 12 and 7 new carbamate derivates were tested in vitro as acetylcholinesterase inhibitors. The tests were performed in the batch stirred reactor at 25°C, pH 8, ionic strength 0.11 M and catalytic activity of the enzyme preparation 0.14 U mL-1 of the reaction mixture. The temporal dependences of actual concentrations of acetylcholine, choline and acetic acid were determined by two independent analytical methods, HPLC and pH-stat. For all used inhibitors, the model of competitive irreversible inhibition was valid. The inhibition rate constant k3 and qualified estimation of the absolute acetylcholinesterase concentration in the reaction mixture were calculated. The partition coefficients Kow between n-octanol and water of all used inhibitors were determined. The k3 and Kow values were correlated with the Hammett and Hansch substituent constants and with the calculated docking and binding energies of the reaction between the tested inhibitors and acetylcholinesterase.
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Cite this article as:
Marketa Kovarova, Mahmud T.H. Khan, Karel Komers, Patrik ParÃk, Alexander Cegan, Martina Zatloukalova , Kinetics of In Vitro Inhibition of Acetylcholinesterase by Nineteen New Carbamates, Current Enzyme Inhibition 2011; 7 (4) . https://dx.doi.org/10.2174/157340811799860560
DOI https://dx.doi.org/10.2174/157340811799860560 |
Print ISSN 1573-4080 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6662 |
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