Frontiers in Chemistry (Feb 2022)

Membrane-Active Antibacterial Agents Based on Calix[4]arene Derivatives: Synthesis and Biological Evaluation

  • Shanfang Fang,
  • Yuan-Ye Dang,
  • Haizhou Li,
  • Hongxia Li,
  • Jiayong Liu,
  • Rongcui Zhong,
  • Yongzhi Chen,
  • Shouping Liu,
  • Shuimu Lin

DOI
https://doi.org/10.3389/fchem.2022.816741
Journal volume & issue
Vol. 10

Abstract

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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.

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