Current Scenario of Pleuromutilin Derivatives with Antibacterial Potential (A Review)

The dramatic increase in antibiotic resistance and the emergence of superbugs have placed renewed emphasis on the importance of development of novel antibacterial agents. Pleuromutilin, a tricyclic diterpene derived from the basidiomycete fungus Clitopilus passeckerianus, could exert the antibacterial activity through inhibition of bacterial protein synthesis by binding to bacterial ribosomes in the peptidyl transferase center of the 50S subunit and inhibiting peptide bond formation. Pleuromutilin derivatives possess potent broad-spectrum activity against diverse pathogenic bacteria, including drug-resistant forms especially methicillin-resistant Staphylococcus aureus (MRSA). Several pleuromutilin derivatives such as retapamulin and lefamulin have already been applied in clinics or are under clinical trials, demonstrating that pleuromutilin derivatives are useful scaffolds for the discovery of novel antibacterial agents. The goal of this review is to highlight the current scenario of pleuromutilin derivatives with antibacterial potential, covering articles published from 2013 to present. The structure-activity relationship of pleuromutilin derivatives is discussed to continuously open up map for the remarkable exploration of more effective candidates.