2. Academic Validation
  3. 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

  • J Antibiot (Tokyo). 2019 Jul;72(7):545-554. doi: 10.1038/s41429-019-0177-9.
Yao Chen 1,  Yuan Ju 2,  Chungen Li 2,  Tao Yang 2,  Yong Deng 3,  Youfu Luo 4
Affiliations

Affiliations

  • 1 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.
  • 2 Cancer Center, West China Hospital, Sichuan University, 610041, Chengdu, China.
  • 3 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. dengyong@scu.edu.cn.
  • 4 Cancer Center, West China Hospital, Sichuan University, 610041, Chengdu, China. luo_youfu@scu.edu.cn.
PMID: 30940910 DOI: 10.1038/s41429-019-0177-9
Abstract

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-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 μg ml-1.

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