Antibacterial oxazolidinones: emerging structure–toxicity relationships

Abstract

The oxazolidinones are an important class of synthetic bacterial protein synthesis inhibitors with activity against Gram-positive and some fastidious Gram-negative bacteria. Key toxicological issues with the class include reversible inhibition of monoamine oxidase enzymes and reversible myelosuppression that can occur in patients treated for longer than the recommended course of therapy. Recent studies have uncovered the likely molecular mechanism underlying oxazolidinone-related myelosuppression and other toxicities, and these will be discussed here. Also reviewed are recent reports of structural modifications that can attenuate one or more of the undesired effects of oxazolidinones, while retaining the desired antibacterial effect.

Keywords::

• mitochondrial protein synthesis inhibition
• monoamine oxidase inhibition
• myelosuppression
• oxazolidinone antibiotics
• protein synthesis inhibitors
• toxicity

Financial & competing interests disclosure

The author has served as a consultant to LegoChem Biosciences. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.