Hubei Key Laboratory of Radiation Chemistry and Functional Materials, School of Nuclear Technology and Chemistry & Biology, Hubei University of Science and Technology, Xian Ning 437100, China.
Curr Top Med Chem. 2021;21(27):2440-2454. doi: 10.2174/1568026620999201113104935.
The increasing danger of methicillin-resistant Staphylococcus aureus (MRSA) and the limited therapeutic options for invasive MRSA infections make an urgent demand for the development of novel anti-MRSA agents. Oxazolidinone derivatives could inhibit protein synthesis by acting on the ribosomal 50S subunit of the bacteria and prevent the formation of a functional 70S initiation complex, so oxazolidinones are a novel class of antimicrobial agents with potential activity against a wide range of clinically significant multidrug-resistant Gram-positive pathogens. However, oxazolidinones such as linezolid are associated with significant adverse events, and myelosuppression represents the main unfavorable side effects. Moreover, MRSA isolates that are resistant to oxazolidinones have already emerged. Hybridization of oxazolidinone with other antibacterial pharmacophores has the potential to interact with multiple targets or to counterbalance the known side effects associated with each pharmacophore. Thus, oxazolidinone-containing hybrids are useful scaffolds for the development of novel anti-MRSA agents. This review covers the recent advances of oxazolidinonecontaining hybrids with anti-MRSA activity developed in the last decade to set up the direction for the design and development of oxazolidinone-containing hybrids with high efficiency and low toxicity.
耐甲氧西林金黄色葡萄球菌（MRSA）的威胁日益增加，而治疗侵袭性 MRSA 感染的方法有限，因此迫切需要开发新型抗 MRSA 药物。恶唑烷酮类衍生物可以通过作用于细菌的核糖体 50S 亚基来抑制蛋白质合成，并阻止功能性 70S 起始复合物的形成，因此恶唑烷酮类是一类具有广泛抗菌活性的新型抗菌药物，对多种临床上重要的耐多药革兰阳性病原体具有潜在活性。然而，像利奈唑胺这样的恶唑烷酮类药物会引起严重的不良反应，骨髓抑制是其主要的不良反应。此外，已经出现了对恶唑烷酮类药物耐药的 MRSA 分离株。将恶唑烷酮与其他抗菌药效团杂交，有可能与多个靶标相互作用，或者抵消每个药效团相关的已知副作用。因此，含恶唑烷酮的杂合体是开发新型抗 MRSA 药物的有用骨架。本综述涵盖了过去十年中开发的具有抗 MRSA 活性的含恶唑烷酮杂合体的最新进展，为设计和开发高效低毒的含恶唑烷酮杂合体指明了方向。
