2. Academic Validation
  3. Structure optimizing of flavonoids against both MRSA and VRE

Structure optimizing of flavonoids against both MRSA and VRE

  • Eur J Med Chem. 2024 May 5:271:116401. doi: 10.1016/j.ejmech.2024.116401.
Mei-Zhen Wei 1,  Yan-Yan Zhu 1,  Wen-Biao Zu 1,  Huan Wang 1,  Li-Yu Bai 1,  Zhong-Shun Zhou 1,  Yun-Li Zhao 1,  Zhao-Jie Wang 1,  Xiao-Dong Luo 2
Affiliations

Affiliations

  • 1 Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, 650500, People's Republic of China.
  • 2 Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, 650500, People's Republic of China; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, People's Republic of China. Electronic address: xdluo@ynu.edu.cn.
PMID: 38640870 DOI: 10.1016/j.ejmech.2024.116401
Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) cause more than 100,000 deaths each year, which need efficient and non-resistant Antibacterial agents. SAR analysis of 162 Flavonoids from the plant in this paper suggested that lipophilic group at C-3 was crucial, and then 63 novel flavonoid derivatives were designed and total synthesized. Among them, the most promising K15 displayed potent bactericidal activity against clinically isolated MRSA and VRE (MICs = 0.25-1.00 μg/mL) with low toxicity and high membrane selectivity. Moreover, mechanism insights revealed that K15 avoided resistance by disrupting biofilm and targeting the membrane, while vancomycin caused 256 times resistance against MRSA, and ampicillin caused 16 times resistance against VRE by the same 20 generations inducing. K15 eliminated residual bacteria in mice skin MRSA-infected model (>99 %) and abdominal VRE-infected model (>92 %), which was superior to vancomycin and ampicillin.

Keywords

Drug-resistance; Flavonoids; MRSA; Membrane disruption; VRE.

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