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Bacterial Nitric Oxide Synthase Inhibition: Designer Drugs to Fight Bad Bugs

  • Author(s): Lewis, Matthew Chancellor
  • Advisor(s): Poulos, Thomas
  • et al.
Creative Commons 'BY-NC-ND' version 4.0 license
Abstract

Antibiotic resistance of pathogenic bacteria is a growing problem of global concern. Current antibiotics target all bacteria indiscriminately and consequently wipe out good, beneficial bacteria as well as the bad, pathogenic ones. Bacterial Nitric Oxide Synthase (bNOS) has been identified as a suitable target to combat Methicilin Resistant Staphylococcus aureus (MRSA), a pathogen responsible for thousands of deaths each year in the United States alone. We report here the development of bNOS selective inhibitors based on an aminoquinolone chemical scaffold. These inhibitors were found to bind in both the active and pterin sites of bNOS, effectively reducing bacterial survival. In addition, we tested the limits of an NO selective chemical probe and began preliminary investigations of other potential drug targets for MRSA related to the NO pathway.

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