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Novel Lawsone-Quinoxaline Hybrids as New Dual Binding Site Acetylcholinesterase Inhibitors.

ABSTRACT: 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 (IC₅₀ = 20 nM) and BChEI (IC₅₀ = 220 nM). The compound 6d did not show cytotoxicity against the SH-SY5Y neuronal cells (GI₅₀ > 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.

SUBMITTER: Suwanhom P

PROVIDER: S-EPMC10500570 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Novel Lawsone-Quinoxaline Hybrids as New Dual Binding Site Acetylcholinesterase Inhibitors.

Suwanhom Paptawan P Nualnoi Teerapat T Khongkow Pasarat P Tipmanee Varomyalin V Lomlim Luelak L

ACS omega 20230829 36

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 (IC50 = 20 nM) and BChEI (IC50 = 220 nM). The compound 6d did not show cytotoxicity against the SH-SY5Y neuronal cells (GI50 > 100 μM). In silico and enzyme kinetic experiments demonstrated that compound 6d bound to both the ...[more]

PMID: 37720764

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