Department of Medicinal Chemistry, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, 610041, Chengdu, China.
Cancer Center, West China Hospital, Sichuan University, 610041, Chengdu, China.
J Antibiot (Tokyo). 2019 Jul;72(7):545-554. doi: 10.1038/s41429-019-0177-9. Epub 2019 Apr 2.
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 μg ml. 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 μg ml.
耐甲氧西林金黄色葡萄球菌（MRSA）感染是一个全球性的健康挑战，因为出现了对几乎所有抗生素类别都具有耐药性的菌株。这就需要迅速开发新型抗菌药物来解决这个关键问题。基于表型的化合物筛选是目前寻找新抗生素的主要策略之一。因此，我们在这里针对 MRSA 进行了表型筛选，发现 NPS-2143 对 MRSA 具有活性，MIC 值为 16μg/ml。为了发现更有效的抗 MRSA 剂，我们设计并合成了一系列 NPS-2143 的衍生物。最有前途的化合物 48 和 49 表现出良好的抗菌活性，MIC 值为 2μg/ml。
