【新一代多环糖肽类抗生素的发明史】。

Q3 Medicine
E N Olsufyeva
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引用次数: 0

摘要

对多环糖肽类抗生素的耐药性增加已成为耐药革兰氏阳性菌感染化疗的一个严重问题。对已知天然抗生素进行化学修饰是研制新一代抗感染药物的主要方向。在过去的二十年里,一系列对革兰氏阳性菌耐药菌株有活性的疏水糖肽类似物被开发出来,其中三种——奥立万星、特拉万星和达尔巴万星于2013-2014年获得美国食品和药物管理局(FDA)批准,用于治疗葡萄球菌和肠球菌敏感和耐药菌株引起的感染。已经证实,糖肽的疏水衍生物可以通过一种不允许与耐药菌的修饰靶标结合的机制作用于耐药菌株。了解天然和修饰的糖肽的作用机制是合理设计具有有价值性质的化合物以获得基本结果的基础。还考虑了使用半合成糖肽类似物对抗包膜病毒引起的病毒感染的可能性。本文综述了新一代抗革兰氏阳性病原体的糖肽抗生素的化学设计的主要途径及其作用机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[History of the Creation of a New Generation of Antibiotics of the Group of Polycyclic Glycopeptides].

Increased resistance to polycyclic glycopeptide antibiotics has become a serious problem for chemotherapy of infections caused by resistant Gram-positive bacteria. Chemical modification of known natural antibiotics is the main direction in the creation of the next generation of anti-infective drugs. Over the past two decades, a series of hydrophobic glycopeptide analogues active against resistant strains of Gram-positive bacteria have been developed, three of which - oritavancin, telavancin, and dalbavancin - were approved by the US Food and Drug Administration (FDA) in 2013-2014 for the treatment of infections caused by sensitive and resistant strains of staphylococci and enterococci. It has been established that hydrophobic derivatives of glycopeptides can act on resistant strains of bacteria by a mechanism that does not allow binding to the modified target of resistant bacteria. Understanding the mechanism of action of natural and modified glycopeptides is considered as the basis for the rational design of compounds with valuable properties to achieve fundamental results. The possibility of using semi-synthetic glycopeptide analogues in the fight against viral infections caused by enveloped viruses is also considered. This review outlines the main ways of chemical design in creating a new generation of glycopeptide antibiotics that overcome resistance to Gram-positive pathogens and the mechanisms of their action.

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来源期刊
Molekulyarnaya Biologiya
Molekulyarnaya Biologiya Medicine-Medicine (all)
CiteScore
0.70
自引率
0.00%
发文量
131
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