硫肽类抗生素诺卡沙星I的结构改造研究进展

Recent Developments in Structural Modification on Thiopeptide Antibiotics of Nocathiacin

诺卡氏菌Nocardia sp.ATCC 202099合成的次级代谢产物诺卡沙星Ⅰ是一种杀菌活性超强,作用靶点和机制新颖的硫肽类抗生素。多年来,诺卡沙星Ⅰ以及其类似物或衍生物一直是新型抗生素开发的热点目标化合物。但是,水溶性差是诺卡沙星Ⅰ成药的关键限制因素。为解决水溶性差的难题,科学家们采取了化学半合成、生物转化以及物理转化的方法对诺卡沙星Ⅰ的结构进行改造,以期增加其水溶性,提高成药性。本文将对诺卡沙星Ⅰ的结构改造进行概述,为水溶性差的抗生素的成药研究提供参考。

The secondary metabolite nocathiacin I synthesized by Nocardia sp.ATCC 202099 was a thiopeptide antibiotic with strong bactericidal activity,and novel target and mechanism.For many years,nocathiacin I and its analogs or derivatives have always been hot target compounds for the development of new antibiotics.However,poor aqueous solubility was a key limiting factorsof proprietary drugs for nocathiacin I.In order to solve the problem of poor aqueous solubility,scientists have adopted chemical semi-synthesis,biotransformation and physical transfer methods to modify the structure of nocathiacin I in order to increase its aqueous solubility and improve the drug-forming properties.In this paper,the structural modification of nocathiacin I would be summarized.It would provide reference for the study of drug preparation of poorly aqueous-soluble antibiotics.