Bisbenzamidine and Bisbenzguanidine Ureas Act as Antibacterial Agents against Pseudomonas aeruginosa.
Bisbenzamidine and Bisbenzguanidine Ureas Act as Antibacterial Agents against Pseudomonas aeruginosa.
复制标题
双苯甲脒和双苯胍脲可作为针对铜绿假单胞菌的抗菌剂。
DOI：
10.1002/cmdc.202300496
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发表时间：
2023
期刊：
影响因子：
3.4
通讯作者：
Wolfe,AmandaL
中科院分区：
文献类型：
--
作者：
Kellogg,CaseyN;Pugh,BryceA;Starr,IsaakM;Parmar,DhruviJ;Troxler,A'ZaneD;Wolfe,AmandaL
由于过去20年来全球抗生素耐药细菌感染数量的增加，迫切需要开发能够克服致病菌耐药机制的小分子抗生素。针对革兰氏阴性病原体（如铜绿假单胞菌）的抗生素开发尤其具有挑战性，因为它们的外膜减少了抗生素的进入。最近，研究表明，广泛的氮功能，包括胍类、脒类、伯胺类、咪唑类和咪唑类，可以促进革兰氏阴性细菌的抗生素和佐剂活性，但很少有这些功能专门针对铜绿假单胞菌，尽管这种病原体被美国疾病控制和预防中心视为严重威胁。在此，我们研究了一系列已知和未知的含氮二聚体，具有胍、脒、二甲基胺和吡啶的功能，对多重耐药铜绿假单胞菌的抗菌活性。我们发现其中两种具有双苯胍和双苯脒功能，对临床分离的多重耐药和形成生物膜的铜绿假单胞菌有效。
Due to the global rise in the number of antibiotic resistant bacterial infections over the past 20 years, there is a dire need for the development of small molecule antibiotics capable of overcoming resistance mechanisms in pathogenic bacteria. Antibiotic development against Gram‐negative pathogens, such asPseudomonas aeruginosa, is especially challenging due to their additional outer membrane which reduces antibiotic entry. Recently, it has been shown that a broad range of nitrogen functionality, including guanidines, amidines, primary amines, imidazolines, and imidazoles, promote antibiotic and adjuvant activity in Gram‐negative bacteria, but few of these have been targeted towardsPseudomonas aeruginosaspecifically despite this pathogen being deemed a critical threat by the United States Centers for Disease Control and Prevention. Herein, we examined a small series of known and unknown nitrogenous dimers, with guanidine, amidine, dimethyl amine, and pyridine functionality, for antibacterial activity against multidrug resistantPseudomonas aeruginosa. We found that two, with bisbenzguanidine and bisbenzamidine functionality, are potent against clinical isolates of multidrug resistant and biofilm formingPseudomonas aeruginosa.