Details

Project TitleNew Bacterial Nitric Oxide Synthase Inhibitors
Track Code2014-182
Short Description

New antibacterial compounds targeting bacterial nitric oxide synthase show promise against resistant bacterial strains 

#therapeutics #infectiousdisease

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital-acquired infections. Furthermore, rates of morbidity and mortality are high among those infected. Recent experiments in S. aureus, B. anthracis and B. subtilis have implicated bacterial nitric oxide synthase (bNOS) as a potential drug target, as it provides the bacterial cell a protective defense mechanism against oxidative stress and select antibiotics. While bNOS and mammalian NOS (mNOS) enzymes bear similarity in their active sites, recent studies suggest that bNOS specificity can be achieved by exploiting significant differences in bNOS pterin-binding and mNOS pterin binding sites. Northwestern scientists have identified and characterized nitric oxide synthase (NOS) inhibitors that function as antimicrobials against MRSA. High-throughput analysis of a variety of NOS inhibitors identified two potent and chemically distinct bNOS inhibitors and both compounds were found to function as antimicrobials against S. aureus. Both compounds bind well to bNOS and exhibit antimicrobial activity as well as promising bNOS selectivity over mNOS isoforms. These results provide the first evidence that NOS inhibitors have the potential to work synergistically with antibiotic-induced oxidative stress to enhance MRSA killing and offer a structural basis for generating other compounds active against this deadly bacterium. 

 
TagsTHERAPEUTICS: infectious disease
 
Posted DateMar 3, 2015 10:40 AM

Inventor(s)

Richard B. Silverman

Soosong Kang

Applications

  • Antibacterial agents

Advantages

  • Effective against Methicillin-resistant Staphylococcus aureus (MRSA)
  • Specific for bacterial NOS enzyme
  • Synergistic with other antibiotics

Publications

IP Status

A provisional patent application has been filed.

Marketing Contact

Vara Josyula, PhD

Invention Manager

(p) 847-491-4456

(e) vara.josyula@northwestern.edu