From Erythromycin to Azithromycin and New Potential Ribosome-Binding Antimicrobials.
From Erythromycin to Azithromycin and New Potential Ribosome-Binding Antimicrobials.
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DOI：
10.3390/antibiotics5030029
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发表时间：
2016-09-01
期刊：
影响因子：
--
通讯作者：
Antolović R
中科院分区：
文献类型：
--
作者：
Jelić D;Antolović R
大环内酯类化合物是一类天然或半合成产物，其抗菌活性主要通过与细菌50 S核糖体亚基的可逆结合和阻断新生蛋白质在细菌蛋白质生物合成中的出口通道而发挥。通常认为是抑菌的，但在较高剂量下也可能是杀菌的。阿奇霉素作为20世纪世纪最重要的新药之一，是一个应用经典构效关系进行药物设计的合理药物化学方法的例子，这将说明一个令人印象深刻的药物发现成功的故事。然而，微生物已经发展了几种机制来获得对抗生素的抗性，包括大环内酯类抗生素。获得细菌对大环内酯类耐药性的主要机制是结合位点的一个或多个核苷酸的突变。虽然报道阿奇霉素对某些物种的核糖体功能的抑制表现出不同的两步过程，但需要更详细地阐述这种特定的作用模式。新的大环衍生物，这可能是更有效的和更不容易逃脱细菌的耐药性机制，也不断进行评估。一类新的抗生素化合物-大环内酯类，其衍生自大环内酯类并包含大环部分、连接基和游离或酯化的喹诺酮3-羧基，对关键的红霉素抗性革兰氏阳性和革兰氏阴性细菌菌株显示出优异的抗菌效力，同时可能降低细菌对大环内酯类的抗性。
Macrolides, as a class of natural or semisynthetic products, express their antibacterial activity primarily by reversible binding to the bacterial 50S ribosomal subunits and by blocking nascent proteins’ progression through their exit tunnel in bacterial protein biosynthesis. Generally considered to be bacteriostatic, they may also be bactericidal at higher doses. The discovery of azithromycin from the class of macrolides, as one of the most important new drugs of the 20th century, is presented as an example of a rational medicinal chemistry approach to drug design, applying classical structure-activity relationship that will illustrate an impressive drug discovery success story. However, the microorganisms have developed several mechanisms to acquire resistance to antibiotics, including macrolide antibiotics. The primary mechanism for acquiring bacterial resistance to macrolides is a mutation of one or more nucleotides from the binding site. Although azithromycin is reported to show different, two-step process of the inhibition of ribosome function of some species, more detailed elaboration of that specific mode of action is needed. New macrocyclic derivatives, which could be more potent and less prone to escape bacterial resistance mechanisms, are also continuously evaluated. A novel class of antibiotic compounds—macrolones, which are derived from macrolides and comprise macrocyclic moiety, linker, and either free or esterified quinolone 3-carboxylic group, show excellent antibacterial potency towards key erythromycin-resistant Gram-positive and Gram-negative bacterial strains, with possibly decreased potential of bacterial resistance to macrolides.
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影响因子：
6.7
作者：
Fajdetic, Andrea;Vinter, Adrijana;Spaventi, Radan
通讯作者：
Spaventi, Radan
DOI：
10.1073/pnas.1008685107
发表时间：
2010-10-05
影响因子：
11.1
作者：
Bulkley, David;Innis, C. Axel;Steitz, Thomas A.
通讯作者：
Steitz, Thomas A.
影响因子：
7.3
作者：
Agouridas, C;Denis, A;Tessot, N
通讯作者：
Tessot, N
影响因子：
5.2
作者：
FOULDS, G;SHEPARD, RM;JOHNSON, RB
通讯作者：
JOHNSON, RB
影响因子：
3.1
作者：
Burnie, JP;Matthews, RC;Hodgetts, SJ
通讯作者：
Hodgetts, SJ