Methicillin-resistant (MRSA) and vancomycin-resistant (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 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 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. eliminated residual bacteria in mice skin MRSA-infected model (>99 %) and abdominal VRE-infected model (>92 %), which was superior to vancomycin and ampicillin.

中文翻译：

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针对 MRSA 和 VRE 的黄酮类化合物的结构优化

耐甲氧西林（MRSA）和耐万古霉素（VRE）每年导致超过10万人死亡，这需要高效且不耐药的抗菌药物。本文对该植物中的162种黄酮类化合物进行了SAR分析，结果表明C-3位点的亲脂基团是关键，进而设计并合成了63种新型黄酮类化合物。其中，最有前途的对临床分离的 MRSA 和 VRE (MIC = 0.25–1.00 μg/mL) 显示出有效的杀菌活性，且毒性低、膜选择性高。此外，机制见解表明，通过破坏生物膜和靶向膜来避免耐药性，而万古霉素对 MRSA 产生了 256 倍的耐药性，而氨苄西林在同样的 20 代诱导下对 VRE 产生了 16 倍的耐药性。消除小鼠皮肤MRSA感染模型（>99%）和腹部VRE感染模型（>92%）残留细菌，效果优于万古霉素和氨苄西林。