截短侧耳素C-14侧链的修饰及其抗菌活性研究进展

Advances in the modification of C-14 side chain and its antibacterial activity of pleuromutilin

抗生素的广泛使用和滥用导致耐药性细菌日益增加。为了应对这种局面,研究人员加大了对抗耐药性细菌抗生素的研发力度。基于此,20世纪50年代,从高等真菌中分离的具有良好抗菌活性的先导化合物截短侧耳素得到了越来越多的关注和研究。构效关系研究表明,截短侧耳素的三环母核结构的改造对抗菌活性的提高作用不大,而对C-14侧链的修饰则可以增加截短侧耳素的抗菌活性和改善其药动学性质。本文就近10年来国内外对截短侧耳素C-14侧链的修饰、抗菌活性和构效关系研究进行综述,并总结了目前研究中存在的问题。

The widespread use and abuse of antibiotics leads to an increasing number of drug-resistant bacteria. In response to this challenge, researchers have taken much efforts to study new antibacterial drugs that could solve the pathogenic bacteria resistance effectively. In this situation, since its good antibacterial activity, the lead compound pleuromutilin isolated from the higher fungi in 1950s has attracted increasing attention at present. The structure-activity relationship research showed that the transformation of the tristate nucleus of pleuromutilin had little effect on the antibacterial activity, while the modification of C-14 side chain could increase the antibacterial activity and improve pharmacokinetic properties. This review summarized the recent progress on the modification of C-14 side chain, antibacterial activities and structure-activity relationship of pleuromutilin over the past 10 years, and also summed up the deficiencies in current researches.