1. Academic Validation
  2. Development of Membrane-Active Honokiol/Magnolol Amphiphiles as Potent Antibacterial Agents against Methicillin-Resistant Staphylococcus aureus (MRSA)

Development of Membrane-Active Honokiol/Magnolol Amphiphiles as Potent Antibacterial Agents against Methicillin-Resistant Staphylococcus aureus (MRSA)

  • J Med Chem. 2021 Sep 9;64(17):12903-12916. doi: 10.1021/acs.jmedchem.1c01073.
Yong Guo 1 2 Enhua Hou 1 Tingyu Wen 1 Xiaoting Yan 1 Meiyue Han 1 Li-Ping Bai 2 Xiangjing Fu 1 Jifeng Liu 1 Shangshang Qin 1
Affiliations

Affiliations

  • 1 School of Pharmaceutical Science, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou 450001, Henan, China.
  • 2 State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa 999078, Macau, China.
Abstract

Currently, infections caused by drug-resistant bacteria have become a new challenge in anti-infective treatment, seriously endangering public health. In our continuous effort to develop new antimicrobials, a series of novel honokiol/magnolol amphiphiles were prepared by mimicking the chemical structures and Antibacterial properties of cationic Antimicrobial Peptides. Among them, compound 5i showed excellent Antibacterial activity against Gram-positive bacteria and clinical MRSA isolates (minimum inhibitory concentrations (MICs) = 0.5-2 μg/mL) with low hemolytic and cytotoxic activities and high membrane selectivity. Moreover, 5i exhibited rapid bactericidal properties, low resistance frequency, and good capabilities of disrupting Bacterial biofilms. Mechanism studies revealed that 5i destroyed Bacterial cell membranes, resulting in Bacterial death. Additionally, 5i displayed high biosafety and potent in vivo anti-infective potency in a murine sepsis model. Our study indicates that these honokiol/magnolol amphiphiles shed LIGHT on developing novel Antibacterial agents, and 5i is a potential Antibacterial candidate for combating MRSA infections.

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