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

被引：101

作者：

Guo, Yong ^{[1
,2
]}

Hou, Enhua ^{[1
]}

Wen, Tingyu ^{[1
]}

Yan, Xiaoting ^{[1
]}

Han, Meiyue ^{[1
]}

Bai, Li-Ping ^{[2
]}

Fu, Xiangjing ^{[1
]}

Liu, Jifeng ^{[1
]}

Qin, Shangshang ^{[1
]}

机构：

[1] Zhengzhou Univ, Sch Pharmaceut Sci, Key Lab Adv Drug Preparat Technol, Minist Educ, Zhengzhou 450001, Henan, Peoples R China

[2] Macau Univ Sci & Technol, Macau Inst Appl Res Med & Hlth, State Key Lab Qual Res Chinese Med, Taipa 999078, Macao, Peoples R China

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2021年 / 64卷 / 17期

基金：

中国国家自然科学基金;

关键词：

DE-NOVO DESIGN; NATURAL-PRODUCTS; ANTIMICROBIAL PEPTIDES; DISCOVERY; HONOKIOL; ANTIBIOTICS; DERIVATIVES; BRILACIDIN; INHIBITORS; BACTERIA;

D O I：

10.1021/acs.jmedchem.1c01073

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 mu g/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.

引用

页码：12903 / 12916

页数：14

共 57 条

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