Bisbenzamidine and Bisbenzguanidine Ureas Act as Antibacterial Agents against Pseudomonas aeruginosa

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,...

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Bibliographic Details
Published in:	ChemMedChem Vol. 18; no. 24; pp. e202300496 - n/a
Main Authors:	Kellogg, Casey N., Pugh, Bryce A., Starr, Isaak M., Parmar, Dhruvi J., Troxler, A'Zane D., Wolfe, Amanda L.
Format:	Journal Article
Language:	English
Published:	Germany Wiley Subscription Services, Inc 14-12-2023
Subjects:	Amines Antibacterial activity Antibacterial agents Antibiotic resistance Antibiotics Bacteria Bacterial diseases Biofilms Clinical isolates dimerization Disease control Gram-negative bacteria Guanidine Guanidines Imidazole Multidrug resistance Pathogens Pseudomonas aeruginosa amines dimerization pseudomonas aeruginosa antibiotics
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Summary:	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 as Pseudomonas 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 towards Pseudomonas aeruginosa specifically 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 resistant Pseudomonas aeruginosa. We found that two, with bisbenzguanidine and bisbenzamidine functionality, are potent against clinical isolates of multidrug resistant and biofilm forming Pseudomonas aeruginosa. Benzamidine and benzguanidine functionality have been found to increase both antibacterial and adjuvant activity of small molecules against Gram‐negative pathogens. Herein, we examine the antibacterial activity of a series of dimeric small molecules with benzamidine, benzguanidine, dimethyl amine, and pyridine moieties against multidrug resistant Pseudomonas aeruginosa.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1860-7179 1860-7187
DOI:	10.1002/cmdc.202300496