Yang Siyu, Liu Fangquan, Leng Yue, Zhang Meiyue, Zhang Lei, Wang Xuekun, Wang Yinhu
State Key Laboratory for Macromolecule Drugs and Large-Scale Manufacturing, School of Pharmaceutical Sciences and Food Engineering, Liaocheng University, Liaocheng 252059, China.
Antibiotics (Basel). 2024 Aug 7;13(8):744. doi: 10.3390/antibiotics13080744.
Infections caused by multidrug-resistant pathogens have emerged as a serious threat to public health. To develop new antibacterial agents to combat such drug-resistant bacteria, a class of novel amphiphilic xanthoangelol-derived compounds were designed and synthesized by mimicking the structure and function of antimicrobial peptides (AMPs). Among them, compound displayed excellent antimicrobial activity against the Gram-positive strains tested (MICs = 0.5-2 μg/mL), comparable to vancomycin, and with low hemolytic toxicity and good membrane selectivity. Additionally, compound demonstrated rapid bactericidal effects, low resistance frequency, low cytotoxicity, and good plasma stability. Mechanistic studies further revealed that compound had good membrane-targeting ability and was able to destroy the integrity of bacterial cell membranes, causing an increase in intracellular ROS and the leakage of DNA and proteins, thus accelerating bacterial death. These results make a promising antimicrobial candidate to combat bacterial infection.
由多重耐药病原体引起的感染已成为对公众健康的严重威胁。为了开发新的抗菌剂来对抗此类耐药细菌，通过模拟抗菌肽（AMPs）的结构和功能，设计并合成了一类新型两亲性黄当归醇衍生化合物。其中，化合物对测试的革兰氏阳性菌株表现出优异的抗菌活性（MICs = 0.5 - 2 μg/mL），与万古霉素相当，且具有低溶血毒性和良好的膜选择性。此外，化合物显示出快速杀菌作用、低耐药频率、低细胞毒性和良好的血浆稳定性。机制研究进一步表明，化合物具有良好的膜靶向能力，能够破坏细菌细胞膜的完整性，导致细胞内活性氧增加以及DNA和蛋白质泄漏，从而加速细菌死亡。这些结果使该化合物成为对抗细菌感染的有前途的抗菌候选物。
