Novel Lawsone–Quinoxaline Hybrids as New Dual Binding Site Acetylcholinesterase Inhibitors

[Image: see text] A new family of lawsone–quinoxaline hybrids was designed, synthesized, and evaluated as dual binding site cholinesterase inhibitors (ChEIs). In vitro tests revealed that compound 6d was the most potent AChEI (IC(50) = 20 nM) and BChEI (IC(50) = 220 nM). The compound 6d did not show...

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Autores principales: Suwanhom, Paptawan, Nualnoi, Teerapat, Khongkow, Pasarat, Tipmanee, Varomyalin, Lomlim, Luelak
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10500570/
https://www.ncbi.nlm.nih.gov/pubmed/37720764
http://dx.doi.org/10.1021/acsomega.3c02683
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author Suwanhom, Paptawan
Nualnoi, Teerapat
Khongkow, Pasarat
Tipmanee, Varomyalin
Lomlim, Luelak
author_facet Suwanhom, Paptawan
Nualnoi, Teerapat
Khongkow, Pasarat
Tipmanee, Varomyalin
Lomlim, Luelak
author_sort Suwanhom, Paptawan
collection PubMed
description [Image: see text] A new family of lawsone–quinoxaline hybrids was designed, synthesized, and evaluated as dual binding site cholinesterase inhibitors (ChEIs). In vitro tests revealed that compound 6d was the most potent AChEI (IC(50) = 20 nM) and BChEI (IC(50) = 220 nM). The compound 6d did not show cytotoxicity against the SH-SY5Y neuronal cells (GI(50) > 100 μM). In silico and enzyme kinetic experiments demonstrated that compound 6d bound to both the catalytic anionic site and the peripheral anionic site of HuAChE. The lawsone–quinoxaline hybrids exhibited potential for further development of potent acetylcholinesterase inhibitors for the treatment of Alzheimer’s disease.
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spelling pubmed-105005702023-09-15 Novel Lawsone–Quinoxaline Hybrids as New Dual Binding Site Acetylcholinesterase Inhibitors Suwanhom, Paptawan Nualnoi, Teerapat Khongkow, Pasarat Tipmanee, Varomyalin Lomlim, Luelak ACS Omega [Image: see text] A new family of lawsone–quinoxaline hybrids was designed, synthesized, and evaluated as dual binding site cholinesterase inhibitors (ChEIs). In vitro tests revealed that compound 6d was the most potent AChEI (IC(50) = 20 nM) and BChEI (IC(50) = 220 nM). The compound 6d did not show cytotoxicity against the SH-SY5Y neuronal cells (GI(50) > 100 μM). In silico and enzyme kinetic experiments demonstrated that compound 6d bound to both the catalytic anionic site and the peripheral anionic site of HuAChE. The lawsone–quinoxaline hybrids exhibited potential for further development of potent acetylcholinesterase inhibitors for the treatment of Alzheimer’s disease. American Chemical Society 2023-08-29 /pmc/articles/PMC10500570/ /pubmed/37720764 http://dx.doi.org/10.1021/acsomega.3c02683 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Suwanhom, Paptawan
Nualnoi, Teerapat
Khongkow, Pasarat
Tipmanee, Varomyalin
Lomlim, Luelak
Novel Lawsone–Quinoxaline Hybrids as New Dual Binding Site Acetylcholinesterase Inhibitors
title Novel Lawsone–Quinoxaline Hybrids as New Dual Binding Site Acetylcholinesterase Inhibitors
title_full Novel Lawsone–Quinoxaline Hybrids as New Dual Binding Site Acetylcholinesterase Inhibitors
title_fullStr Novel Lawsone–Quinoxaline Hybrids as New Dual Binding Site Acetylcholinesterase Inhibitors
title_full_unstemmed Novel Lawsone–Quinoxaline Hybrids as New Dual Binding Site Acetylcholinesterase Inhibitors
title_short Novel Lawsone–Quinoxaline Hybrids as New Dual Binding Site Acetylcholinesterase Inhibitors
title_sort novel lawsone–quinoxaline hybrids as new dual binding site acetylcholinesterase inhibitors
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10500570/
https://www.ncbi.nlm.nih.gov/pubmed/37720764
http://dx.doi.org/10.1021/acsomega.3c02683
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