Photoactivated chalcogenylation enables the synthesis of chalcogenyl-DHB derivatives with relevant MAO-A inhibitory activity

Abstract

In the present work, we report a planned and sustainable photoactivated protocol for the synthesis of chalcogenylated 2,3-dihydrobenzofuran (DHB) derivatives along with experimental approaches to evaluate their potential inhibitory activity against monoamine oxidase (MAO)-A. Using blue-light irradiation and carbon tetrabromide as a mediator, a series of sulfur-, selenium-, and tellurium-based DHB hybrids was strategically designed and efficiently obtained under mild, metal-free conditions. The methodology exhibits broad functional-group tolerance and allows rapid generation of structurally diverse derivatives in moderate to good yields. All compounds were fully characterized by NMR and mass spectrometry, with additional GC–MS analysis performed when necessary. Their potential as MAO-A inhibitors was evaluated in vitro, revealing several active derivatives. Molecular docking studies supported these findings, showing favorable interactions within the MAO-A active site. ADMET predictions indicated suitable pharmacokinetic profiles and low to moderate safety concerns. Overall, this work demonstrates that rationally designed photoinduced chalcogenylation is an effective approach for accessing biologically relevant DHB hybrids, highlighting their promise as candidates for the development of novel MAO-A inhibitors