Shinabarger D
Pharmacia & Upjohn, 7000 Portage Road, Kalamazoo, Michigan, USA.
Expert Opin Investig Drugs. 1999 Aug;8(8):1195-202. doi: 10.1517/13543784.8.8.1195.
Oxazolidinones represent a new class of synthetic antibacterial agents active against multiply-resistant Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant streptococci and vancomycin-resistant enterococci. Eperezolid and linezolid are two novel analogues, which have respectively completed Phase I and Phase II clinical testing. The lack of cross-resistance between oxazolidinones and other antibiotics supports a novel mechanism of action. Oxazolidinones are protein synthesis inhibitors which target an early step involving the binding of N-formylmethionyl-tRNA to the ribosome. Binding studies demonstrate that these agents interact with the 50S subunit, but not the 30S subunit of the ribosome. Crosslinking experiments provide evidence for an interaction with both the 16S rRNA of the small subunit and the 23S rRNA of the large subunit. Development of resistance in the laboratory is slow, resulting in two independently isolated point mutations at G2447U and G2576U of the 23S rRNA. This review discusses the results of published studies involving oxazolidinone mechanism of action.
恶唑烷酮类是一类新型合成抗菌剂，对多重耐药革兰氏阳性病原体具有活性，包括耐甲氧西林金黄色葡萄球菌（MRSA）、耐青霉素链球菌和耐万古霉素肠球菌。依哌唑胺和利奈唑胺是两种新型类似物，分别已完成I期和II期临床试验。恶唑烷酮类与其他抗生素之间缺乏交叉耐药性，这支持了一种新的作用机制。恶唑烷酮类是蛋白质合成抑制剂，其作用靶点是N-甲酰甲硫氨酰-tRNA与核糖体结合这一早期步骤。结合研究表明，这些药物与核糖体的50S亚基相互作用，而不与30S亚基相互作用。交联实验为与小亚基的16S rRNA和大亚基的23S rRNA均存在相互作用提供了证据。在实验室中耐药性的产生较为缓慢，导致在23S rRNA的G2447U和G2576U处出现两个独立分离的点突变。本综述讨论了已发表的涉及恶唑烷酮类作用机制研究的结果。
