The evolving role of chemical synthesis in antibacterial drug discovery.
The evolving role of chemical synthesis in antibacterial drug discovery.
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DOI：
10.1002/anie.201310843
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发表时间：
2014-08-18
期刊：
影响因子：
--
通讯作者：
Myers AG
中科院分区：
文献类型：
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作者：
Wright PM;Seiple IB;Myers AG
世纪早期抗生素的发现和应用改变了人类的健康和福祉。化学合成使第一批抗菌物质、有机砷和磺胺药物得以发展，但这些药物很快就被自然界中许多更强大、更复杂的抗生素所超越：青霉素、链霉素、四环素和红霉素等。这些主要防御现在明显不那么有效，这是病原菌内迅速进化的耐药性的不可避免的结果，抗生素的广泛滥用使情况变得更糟。几十年来，药物化学家通过半合成和较小程度的全合成途径补充了抗生素的武库，但经济因素导致这种努力的消退，这将社会置于灾难的边缘。我们认为，如果要避免全球范围的危机，现代化学合成在抗菌药物发现中的战略应用必须发挥关键作用。
The discovery and implementation of antibiotics in the early twentieth century transformed human health and wellbeing. Chemical synthesis enabled the development of the first antibacterial substances, organoarsenicals and sulfa drugs, but these were soon outshone by a host of more powerful and vastly more complex antibiotics from nature: penicillin, streptomycin, tetracycline, and erythromycin, among others. These primary defences are now significantly less effective as an unavoidable consequence of rapid evolution of resistance within pathogenic bacteria, made worse by widespread misuse of antibiotics. For decades medicinal chemists replenished the arsenal of antibiotics by semisynthetic and to a lesser degree fully synthetic routes, but economic factors have led to a subsidence of this effort, which places society on the precipice of a disaster. We believe that the strategic application of modern chemical synthesis to antibacterial drug discovery must play a critical role if a crisis of global proportions is to be averted.