Optimization and Lead Selection of Novel Antimycobacterial Agents

DESCRIPTION (provided by applicant): The non-tuberculous mycobacteria (NTM) are a growing public health concern as the number of opportunistic infections increases. Although not a reportable disease, there is growing epidemiologic evidence to suggest thatNTM cause more infections today in the United States than Mycobacterium tuberculosis (Mtb) yet, unlike Mtb, there are few dedicated antimicrobial drug discovery programs specifically for NTM. Pulmonary disease caused by NTM is especially problematic in patients with underlying susceptibilities such as immunosuppressive medications, cystic fibrosis and other lung diseases, HIV and malignancies. Given the emergence of NTM as a public health issue, finding new antibacterial agents is of high importance. We have screened libraries of novel compounds for anti-NTM activity, focusing on M. abscessus, and have found several promising hits centered around three chemically tractable small molecule scaffolds that exhibit minimal cytotoxicity. The minimum inhibito