Exploring the 1-(4-Nitrophenyl)-3-arylprop-2-en-1-one Scaffold for the Selective Inhibition of Monoamine Oxidase B

ACS Med Chem Lett. 2024 Sep 27;15(10):1685-1691. doi: 10.1021/acsmedchemlett.4c00246. eCollection 2024 Oct 10.

Abstract

A small library of 1-(4-nitrophenyl)-3-arylprop-2-en-1-one derivatives was synthesized to identify new human monoamine oxidase B selective inhibitors. Their inhibitory activity toward MAO-A and MAO-B isoforms was evaluated to determine their potency and selectivity. All newly synthesized compounds were nanomolar inhibitors of the B isoform with IC50 concentrations ranging from 120 to 2.2 nM. Conversely, their activity toward the A isozyme was only observed at micromolar concentrations. Our results bear out the hypothesis that the 1,3-diarylpropenone scaffold could represent a valuable starting point for designing efficient and selective MAO-B inhibitors.