Antibacterial oxazolidinones: emerging structure-toxicity relationships.
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.
Renslo
Adam R
AR
Department of Pharmaceutical Chemistry and the Small Molecule Discovery Center, University of California, San Francisco, 1700 4th Street, San Francisco, CA 94158, USA. adam.renslo@ucsf.edu
D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000737:chemistry* / Q000494:pharmacology; D006095:Gram-Positive Cocci / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors; D008995:Monoamine Oxidase / Q000187:drug effects; D023303:Oxazolidinones / Q000009:adverse effects* / Q000737:chemistry* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D024101:Mitochondrial Proteins; D023303:Oxazolidinones; D008995:Monoamine Oxidase