噁唑烷酮—喹诺酮杂合物的研究进展

Advances on Oxazolidinone-quinolone Hybrids

由于细菌耐药现象的日益严重,近些年来对新型抗菌药的需求不断增长。利用拼合原理将两种药物通过一定的方式连接而成的多靶点杂合物,为扩大药物的抗菌谱、增强药物对耐药菌的有效性及降低耐药性的出现提供了可能,已成为研发新型抗菌药物的一种新策略。与此同时,噁唑烷酮类和喹诺酮类抗菌药以其独特的作用机制和抗菌谱互补的特点吸引了研究者的关注,因此他们将这两类抗菌药物的药效基团进行拼合形成了一系列的噁唑烷酮—喹诺酮杂合物,并已表明它们对多种敏感和耐药菌株均有活性。本文就此类杂合物的设计合成、抗菌活性及目前处于临床研究阶段的噁唑烷酮—喹诺酮杂合物——咔哒唑胺的研究进展作一综述。

Due to the increasing severity of bacterial drug resistance, the demand for novel antimicrobial agents has been growing in recent years. The multi-target hybrid which combines two kinds of drugs by a certain way provides the possibility for expanding the antibacterial spectrum, enhancing the activity against drug-resistant bacteria and reducing the frequency of bacterial re- sistance, and has become a new strategy to the research and development of novel antimicrobial a- gents. Meanwhile, oxazolidinones and quinolones with their unique mechanism of action and the complementary antibacterial spectrum attract the attention of researchers. Oxazolidinone-quinolone hybrids incorporating oxazolidinone and quinolone pharmacophores have been synthesized and shown to be active against a variety of susceptible and resistant Gram-positive and Gram-negative bacteria. In the present paper, the design, synthesis and antimierobial activities of oxazolidinonequinolone hybrids, and the research progress of cadazolid, a oxazolidinone-quinolone hybrid which is currently at the stage of clinical trials, are reviewed.