title: Small-molecule suppression of β-lactam resistance in multidrug-resistant gram-negative pathogens.
abstract: Recent efforts toward combating antibiotic resistance in bacteria have focused on Gram-positive bacteria; however, multidrug-resistant Gram-negative bacteria pose a significant risk to public health. An orthogonal approach to the development of new antibiotics is to develop adjuvant compounds that enhance the susceptibility of drug-resistant strains of bacteria to currently approved antibiotics. This paper describes the synthesis and biological activity of a library of aryl amide 2-aminoimidazoles based on a lead structure from an initial screen. A small molecule was identified from this library that is capable of lowering the minimum inhibitory concentration of β-lactam antibiotics by up to 64-fold.
authors.affiliation: Department of Chemistry and ‡Department of Molecular and Structural Biochemistry, North Carolina State University , Raleigh, North Carolina 27695, United States.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Brackett
authors.forename: Roberta J
authors.initials: RJ
authors.lastname: Melander
authors.forename: Il Hwan
authors.initials: IH
authors.lastname: An
authors.forename: Aparna
authors.initials: A
authors.lastname: Krishnamurthy
authors.forename: Richele J
authors.initials: RJ
authors.lastname: Thompson
authors.forename: John
authors.initials: J
authors.lastname: Cavanagh
authors.forename: Christian
authors.initials: C
authors.lastname: Melander
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D006090:Gram-Negative Bacteria / Q000145:classification / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D012756:Sheep; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D018440:beta-Lactam Resistance / Q000187:drug effects*
chemical_list: D054852:Small Molecule Libraries