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

ABSTRACT: Multitarget directed ligands (MTDLs) represent a promising frontier in tackling the complexity of multifactorial pathologies. The synergistic inhibition of monoamine oxidase B (MAO B) and acetylcholinesterase (AChE) is believed to provide a potentiated effect in the treatment of Alzheimer's disease. Among previously reported micromolar or sub-micromolar coumarin-bearing dual inhibitors, compound 1 returned a tight-binding inhibition of MAO B (K _i = 4.5 μM) and a +5.5 °C increase in the enzyme T _m value. Indeed, the X-ray crystal structure revealed that binding of 1 produces unforeseen conformational changes at the MAO B entrance cavity. Interestingly, 1 showed great shape complementarity with the AChE enzymatic gorge, being de

SUBMITTER: Ekstrom F 

PROVIDER: S-EPMC8919507 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature