Coumarin Derivative Hybrids: Novel Dual Inhibitors Targeting Acetylcholinesterase and Monoamine Oxidases for Alzheimer's Therapy.

ABSTRACT: Multi-target-directed ligands (MTDLs) represent a promising frontier in tackling the complexity of multifactorial pathologies like Alzheimer's disease (AD). The synergistic inhibition of MAO-B, MAO-A, and AChE is believed to enhance treatment efficacy. A novel coumarin-based molecule substituted with O-phenylpiperazine via three- and four-carbon linkers at the 5- and 7-positions, has been identified as an effective MTDL against AD. Employing a medicinal chemistry approach, combined with molecular docking, molecular dynamic simulation, and ΔG_bind estimation, two series of derivatives emerged as potent MTDLs: 8-acetyl-7-hydroxy-4-methylcoumarin (IC₅₀: 1.52-4.95 μM for hAChE, 6.97-7.65 μM for hMAO-A) and 4,7-dimethyl-5-hydroxycoumarin (IC₅₀: 1.88-4.76 μ

SUBMITTER: Zolek T 

PROVIDER: S-EPMC11641184 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature