Small-molecule suppression of β-lactam resistance in multidrug-resistant gram-negative pathogens
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.
Brackett, CM., Melander, RJ., An, IH., Krishnamurthy, A., Thompson, RJ., Cavanagh, J., & Melander, C. (2014). Small-molecule suppression of β-lactam resistance in multidrug-resistant gram-negative pathogens. Journal of Medicinal Chemistry, 57(17), 7450-7458. DOI: 10.1021/jm501050e