Design, synthesis, and evaluation of 1, 3-dioxo-<i>N-</i>phenylisoindoline-5-carboxamide derivatives as potent reversible inhibitors of human monoamine oxidase B with neuroprotective properties.

ABSTRACT: A series of 1, 3-dioxo-N-phenylisoindoline-5-carboxamide derivatives were designed, synthesised and evaluated as potent human monoamine oxidase B (hMAO-B) inhibitors with neuroprotective properties. The structure-activity relationship (SAR) was summarised. The most potent compound identified in the study, compound 16, exhibited significant hMAO-B inhibition (IC₅₀ = 0.011 μM) and remarkable selectivity (selectivity index > 3636) over hMAO-A. Kinetic analysis confirmed that compound 16 acted as a mixed-type, reversible hMAO-B inhibitor. Molecular docking studies provided insights into the interactions between the inhibitor and the enzyme. In cellular assays, compound 16 significantly reduced the production of nitric oxide (NO

SUBMITTER: Mu M 

PROVIDER: S-EPMC12613308 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature