铜绿假单胞菌
抗菌剂
金黄色葡萄球菌
生物膜
微生物学
多重耐药
化学
抗生素
抗生素耐药性
抗菌肽
耐甲氧西林金黄色葡萄球菌
细菌
肺炎
皮肤感染
生物
医学
内科学
遗传学
作者
Xiaomin Guo,Tiantian Yan,Jing Rao,Yingying An,Yue Xin,Xiaokang Miao,Rui Wang,Wangsheng Sun,Jianfeng Cai,Junqiu Xie
标识
DOI:10.1021/acs.jmedchem.2c01396
摘要
The prevalence of multidrug-resistant bacterial infections has led to dramatically increased morbidity and mortality. Antimicrobial peptides (AMPs) have great potential as new therapeutic agents to reverse this dangerous trend. Herein, a series of novel AMP Feleucin-K3 analogues modified with unnatural peptidomimetic sulfono-γ-AA building blocks were designed and synthesized. The structure–activity, structure–toxicity, and structure–stability relationships were investigated to discover the optimal antimicrobial candidates. Among them, K122 exhibited potent and broad-spectrum antimicrobial activity and high selectivity. K122 had a rapid bactericidal effect and a low tendency to induce resistance. Surprisingly, K122 showed excellent effectiveness against bacterial pneumonia. For biofilm and local skin infections, K122 significantly decreased the bacterial load and improved tissue injury at a dose of only 0.25 mg/kg, which was 160 times lower than the concentration deemed to be safe for local dermal applications. In summary, K122 is an outstanding candidate for the treatment of multidrug-resistant bacteria and biofilm infections.
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