Synthesis and Biological Activities of Oxazolidinone Pleuromutilin Derivatives as a Potent Anti-MRSA Agent

Abstract

A series of pleuromutilin derivatives containing an oxazolidinone skeleton were synthesized and evaluated in vitro and in vivo as antibacterial agents. Most of the synthesized derivatives exhibited potent antibacterial activities against three strains of Staphylococcus aureus (including MRSA ATCC 33591, MRSA ATCC 43300, and MSSA ATCC 29213) and two strains of Staphylococcus epidermidis (including MRSE ATCC 51625 and MSSE ATCC 12228). Compound 28 was the most active antibacterial agent in vitro (MIC = 0.008−0.125 μg•mL −1 ) and exhibited a significant bactericidal effect, low cytotoxicity, and weak inhibition (IC 50 = 20.66 μmol•L −1 ) for CYP3A4, as well as exhibited less possibility to cause bacterial resistance. Furthermore, in vivo activities indicated that the compound was effective in reducing MRSA load in a murine thigh infection model. Moreover, it clearly facilitated the healing of MRSA skin infection and inhibited the secretion of the TNF-α, IL-6, and MCP-1 inflammatory factors in serum. These results suggest that oxazolidinone pleuromutilin is a promising therapeutic candidate for drug-resistant bacterial infections.

Microfluidic‐based nanoemulsion of Ocimum basilicum extract: Constituents, stability, characterization, and potential biomedical applications for improved antimicrobial and anticancer properties

“…The advancement of healthcare relies heavily on the emergence of new scientific disciplines, as they foster innovation, provide profound insights into diseases, and introduce fresh solutions to enhance patient outcomes (Chen et al, 2020; Li et al, 2023; Wang et al, 2021; Xia et al, 2023). O. basilicum extract has a rich history spanning thousands of years and has been utilized in various fields such as food preservation, pharmaceuticals, alternative medicine, and natural therapies.…”

Micro-arc oxidation (MAO) and its potential for improving the performance of titanium implants in biomedical applications

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Design and Synthesis of Pleuromutilin Derivatives as Antibacterial Agents Using Quantitative Structure–Activity Relationship Model

“…After the discovery of pleuromutilin in 1951, tremendous efforts have been made to modify its scaffold to explore the structure-activity relationship (SAR) [9]. Modification of the pleuromutilin tricyclic ring does not improve their antibacterial activities significantly [10]. However, the presence of a thioether group at the side chain of pleuromutilin and a basic group enhances antibacterial activity dramatically [11].…”