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2,4-Diacetylphloroglucinol (DAPG) derivatives rapidly eradicate methicillin-resistant staphylococcus aureus without resistance development by disrupting membrane
Zhong, Yifan1; He, Xiaoli2,3; Tao, Wenlan2,3; Feng, Jizhou1; Zhang, Ruixue1; Gong, Hongzhi1; Tang, Ziyi2,3; Huang, Chao1; He, Yun1,2,4
2023-12-05
摘要Methicillin-resistant Staphylococcus aureus (MRSA) causes severe public health challenges throughout the world, and the multi-drug resistance (MDR) of MRSA to antibiotics necessitates the development of more effective antibiotics. Natural 2,4-diacetylphloroglucinol (DAPG), produced by Pseudomonas, displays moderate inhibitory activity against MRSA. A series of DAPG derivatives was synthesized and evaluated for their antibacterial activities, and some showed excellent activities (MRSA MIC = 0.5-2 mu g/mL). Among these derivatives, 7g demonstrated strong antibacterial activity without resistance development over two months. Mechanistic studies suggest that 7g asserted its activity by targeting bacterial cell membranes. In addition, 7g exhibited significant synergistic antibacterial effects with oxacillin both in vitro and in vivo, with a tendency to eradicate MRSA biofilms. 7g is a promising lead for the treatment of MRSA.
关键词4-Diacetylphloroglucinol MRSA Antimicrobial resistance Cell membrane Synergy Biofilm
DOI10.1016/j.ejmech.2023.115823
发表期刊EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
ISSN0223-5234
卷号261页码:18
通讯作者Huang, Chao(chuang@cqu.edu.cn) ; He, Yun(yun.he@cqu.edu.cn)
收录类别SCI
WOS记录号WOS:001094793400001
语种英语