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

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.

Skeletal Editing via Transition-Metal-Catalyzed Nitrene Insertion.

Metal-nitrenes are valuable reactive intermediates for synthesis and are widely used to construct biologically relevant scaffolds, complexes and functionalized molecules. The ring expansion of cyclic molecules via single-nitrogen-atom insertion via nitrene or metal-nitrenoid intermediates has emerged as a promising modern strategy for driving advantageous nitrogen-rich compound synthesis. In recent years, the catalytic insertion of a single nitrogen atom into carbocycles, leading to N-heterocycles, has become an important focus of modern synthetic approaches with applications in medicinal chemistry, materials science, and industry.