Optimizing Linezolid: Transforming It into a Selective MAO-B Inhibitor via a Toxicity-to-Activity Optimization Approach.

ABSTRACT: Linezolid, a widely used oxazolidinone antibiotic, exhibits potent activity against resistant bacterial infections but is associated with serotonergic toxicity, primarily due to its inhibition of monoamine oxidase (MAO). MAOs, consisting of MAO-A and MAO-B isoforms, play crucial roles in neurotransmitter metabolism, with implications for neurodegenerative disorders like Parkinson's and Alzheimer's diseases. This study aims to optimize Linezolid's structure to transform it into a selective MAO-B inhibitor. Utilizing structure-activity and structure-toxicity relationship approaches, novel analogues of Linezolid were synthesized by replacing its oxazolidinone ring with a thiadiazole scaffold. Among the synthesized compounds, 6b emerged as a lead candidate, displaying a remarkable MAO-B

SUBMITTER: Dhangar MS 

PROVIDER: S-EPMC11726377 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature