New resorcylic acid derivatives of Lysimachia tengyuehensis against MRSA and VRE by interfering with bacterial metabolic imbalance.

Eur J Med Chem

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:

Published: November 2024

AI Article Synopsis

  • The misuse of antibiotics has caused a worrying increase in bacterial resistance, jeopardizing human health, prompting researchers to isolate 8 resorcylic acid derivatives from Lysimachia tengyuehensis, which show effectiveness against MRSA and VRE.
  • Two of these compounds rapidly kill MRSA and VRE within 40 minutes and maintain effectiveness without developing drug resistance for 20 days, highlighting their potential as new treatments.
  • The compounds work by disrupting bacterial biofilms and cell membranes due to specific structural features, and they have shown promise in treating MRSA-infected skin wounds and VRE-infected peritoneal infections in living organisms.

Article Abstract

The abuse of antibiotics leads to the rapid spread of bacterial resistance, which seriously threatens human life and health. Now, 8 resorcylic acid derivatives, including 4 new compounds (1-4) were isolated from Lysimachia tengyuehensis by bio-guided isolation, and they inhibited both methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) (MIC = 4-8 μg/mL). Notably, 1 and 2 rapidly killed MRSA and VRE within 40 min without drug resistance in 20 days. Mechanically, they potently disrupted biofilm and cell membrane by interfering with bacterial metabolic imbalance. The structure-activity relationship (SAR) revealed that the lipophilic long carbon chains (C-5/C-6) and hydrophilic hydroxyl/carboxyl groups were essential for the anti-MRSA and VRE bioactivity. Additionally, they effectively recovered MRSA-infected skin wounds and VRE-infected peritoneal in vivo. Resorcylic acid derivatives showed significant anti-MRSA and VRE bioactivity in vitro and in vivo with potential application for the first time.

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Source
http://dx.doi.org/10.1016/j.ejmech.2024.116714DOI Listing

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