%A Fang,Shanfang %A Dang,Yuan-Ye %A Li,Haizhou %A Li,Hongxia %A Liu,Jiayong %A Zhong,Rongcui %A Chen,Yongzhi %A Liu,Shouping %A Lin,Shuimu %D 2022 %J Frontiers in Chemistry %C %F %G English %K Antimicrobial agents,Calix[4]arene derivatives,membrane-active,Peptidomimetics,Bacterial resistance,Gram-Positive Bacteria %Q %R 10.3389/fchem.2022.816741 %W %L %M %P %7 %8 2022-February-08 %9 Original Research %# %! Membrane-Active Antibacterial Agents %* %< %T Membrane-Active Antibacterial Agents Based on Calix[4]arene Derivatives: Synthesis and Biological Evaluation %U https://www.frontiersin.org/articles/10.3389/fchem.2022.816741 %V 10 %0 JOURNAL ARTICLE %@ 2296-2646 %X 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 (16) 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 16 can destroy bacterial cell membrane directly, leading to bacterial death and a low tendency to develop bacterial resistance.