Pyridine-2,6-Dithiocarboxylic Acid and Its Metal Complexes: New Inhibitors of New Delhi Metallo β-Lactamase-1

Carbapenem-resistant Enterobacteriaceae continue to threaten human health worldwide with few effective treatment options. New Delhi metallo-β-lactamase (NDM) enzymes are a contributing element that drive resistance to many β-lactam- and carbapenem-based antimicrobials. Many NDM inhibitors are known,...

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Detalles Bibliográficos
Autores principales: Thomas, Chris S., Braun, Doug R., Olmos, Jose Luis, Rajski, Scott R., Phillips, George N., Andes, David, Bugni, Tim S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374359/
https://www.ncbi.nlm.nih.gov/pubmed/32498259
http://dx.doi.org/10.3390/md18060295
Descripción
Sumario:Carbapenem-resistant Enterobacteriaceae continue to threaten human health worldwide with few effective treatment options. New Delhi metallo-β-lactamase (NDM) enzymes are a contributing element that drive resistance to many β-lactam- and carbapenem-based antimicrobials. Many NDM inhibitors are known, yet none are clinically viable. In this study, we present and characterize a new class of NDM-1 inhibitors based on a pyridine-2,6-dithiocarboxylic acid metal complex scaffold. These complexes display varied and unique activity profiles against NDM-1 in kinetic assays and serve to increase the effectiveness of meropenem, an established antibacterial, in assays using clinical Enterobacteriaceae isolates.

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