Bisbenzamidine and Bisbenzguanidine Ureas Act as Antibacterial Agents against Pseudomonas aeruginosa

Author:

Kellogg Casey N.1ORCID,Pugh Bryce A.1,Starr Isaak M.1,Parmar Dhruvi J.1,Troxler A'Zane D.1,Wolfe Amanda L.1ORCID

Affiliation:

1. Chemistry and Biochemistry University of North Carolina Asheville One University Heights Asheville NC-28804 USA

Abstract

AbstractDue 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.

Publisher

Wiley

Subject

Organic Chemistry,General Pharmacology, Toxicology and Pharmaceutics,Molecular Medicine,Drug Discovery,Biochemistry,Pharmacology

Reference21 articles.

1.  

2. Centers for Disease Control and Prevention (U. S.).Antibiotic Resistance Threats in the United States 2019 Centers for Disease Control and Prevention (U. S.).

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5. The Epidemiology and Pathogenesis and Treatment of Pseudomonas aeruginosa Infections: An Update

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