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Dual Reversible Coumarin Inhibitors Mutually Bound to Monoamine Oxidase B and Acetylcholinesterase Crystal Structures

Fredrik Ekström, Andrea Gottinger, Nina Forsgren, Marco Catto, L.G. Iacovino, Leonardo Pisani, Claudia Binda

2022ACS Medicinal Chemistry Letters32 citationsDOIOpen Access PDF

Abstract

showed great shape complementarity with the AChE enzymatic gorge, being deeply buried from the catalytic anionic subsite (CAS) to the peripheral anionic subsite (PAS) and causing significant structural changes in the active site. These findings provide structural templates for further development of dual MAO B and AChE inhibitors.

Topics & Concepts

AcetylcholinesteraseMonoamine oxidaseCoumarinChemistryMonoamine oxidase BStereochemistryMonoamine oxidase AEnzymeMonoamine neurotransmitterActive siteBinding siteBiochemistryReceptorOrganic chemistrySerotoninCholinesterase and Neurodegenerative DiseasesChemical synthesis and alkaloidsComputational Drug Discovery Methods