Fang Shanfang, Dang Yuan-Ye, Li Haizhou, Li Hongxia, Liu Jiayong, Zhong Rongcui, Chen Yongzhi, Liu Shouping, Lin Shuimu
The Fifth Affiliated Hospital and Key Laboratory of Molecular Target and Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, China.
Front Chem. 2022 Feb 8;10:816741. doi: 10.3389/fchem.2022.816741. eCollection 2022.
Bacteria have developed increasing resistance to currently used antimicrobial agents. New classes of antimicrobial drugs are urgently required to fight drug-resistant pathogens. Here, we designed and synthesized a series of calix[4]arene derivatives as antibacterial agents by biomimicking the structural properties and biological functions of antibacterial peptides. After introducing cationic hydrophilic moieties and preliminary structural optimization, we obtained a lead compound () that exhibited excellent antibacterial activity against Gram-positive bacteria, low toxicity toward mammalian cells and poor hemolytic activity. The antibacterial mechanism studies showed that compound can destroy bacterial cell membrane directly, leading to bacterial death and a low tendency to develop bacterial resistance.
细菌对目前使用的抗菌剂的耐药性日益增强。迫切需要新型抗菌药物来对抗耐药病原体。在此，我们通过模拟抗菌肽的结构特性和生物学功能，设计并合成了一系列杯[4]芳烃衍生物作为抗菌剂。在引入阳离子亲水基团并进行初步结构优化后，我们获得了一种先导化合物（），它对革兰氏阳性菌表现出优异的抗菌活性，对哺乳动物细胞毒性低，溶血活性差。抗菌机制研究表明，该化合物可直接破坏细菌细胞膜，导致细菌死亡，且产生细菌耐药性的倾向较低。
