Discovery of novel N-(prop-2-yn-1-yl)-1,2,3,4-tetrahydronaphthalen-1-amine derivatives as MAO-B inhibitors for the treatment of Parkinson's disease.

ABSTRACT: Monoamine oxidase B (MAO-B) inhibitors may be an effective therapeutic approach for Parkinson's disease. This study designed and synthesised a series of N-(prop-2-yn-1-yl)-1,2,3,4-tetrahydronaphthalen-1-amine derivatives and evaluated their inhibitory activity against human MAO-B (hMAO-B). Most compounds exhibited inhibitory activity and selectivity, with compounds 29 and 34 demonstrating the strongest inhibitory potency (IC₅₀ = 0.066 ± 0.03 μM and 0.070 ± 0.002 μM, respectively) and selectivity indices (SI > 151 and 134), which were superior to the positive control rasagiline. Enzyme kinetic studies confirmed that these representative active compounds exhibited mixed reversible inhibition of hMAO-B. Molecular docking and kinetic analyses indicated that compound

SUBMITTER: Wang Z 

PROVIDER: S-EPMC12784640 | biostudies-literature | 2026 Dec

REPOSITORIES: biostudies-literature