Design, synthesis, and antibacterial evaluation of novel derivatives of NPS-2143 for the treatment of methicillin-resistant S. aureus (MRSA) infection
Design, synthesis, and antibacterial evaluation of novel derivatives of NPS-2143 for the treatment of methicillin-resistant S. aureus (MRSA) infection
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DOI：
10.1038/s41429-019-0177-9
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发表时间：
2019-07-01
影响因子：
3.3
通讯作者：
Luo, Youfu
中科院分区：
文献类型：
--
作者：
Chen, Yao;Ju, Yuan;Luo, Youfu
耐甲氧西林金黄色葡萄球菌（MRSA）感染是一个重大的全球健康挑战，因为出现了对几乎所有类别的抗生素都表现出耐药性的菌株。这就需要快速开发新的抗菌剂来解决这一关键问题。基于表型筛选化合物是目前发现新抗生素的主要策略之一。因此，我们在这里进行了针对MRSA的表型筛选，并鉴定出具有抗MRSA活性的NPS-2143，其MIC值为16 μ g ml（-1）。为了发现更有效的抗MRSA药物，设计并合成了一系列的抗MRSA药物。最有希望的化合物48和49显示出良好的抗微生物活性，MIC值为2 μ g/ml。
Methicillin-resistant Staphylococcus aureus (MRSA) infections are a significant global health challenge due to the emergence of strains exhibiting resistance to nearly all classes of antibiotics. This necessitates the rapid development of novel antimicrobials to circumvent this critical problem. Screening of compounds based on phenotypes is one of the major strategies for finding new antibiotics at present. Hence, we here performed a phenotypic screening against MRSA and identified NPS-2143 exhibiting activity against MRSA with an MIC value of 16 mu g ml(-1). In order to discover more potent anti-MRSA agents, a series of derivatives of NPS-2143 were designed and synthesized. The most promising compounds 48 and 49 exhibited favorable antimicrobial activity with an MIC value of 2 mu g ml(-1).