Pathology

Mycobacterium tuberculosis

Moxifloxacin

Vancomycin

Staphylococcus aureus

Bedaquiline

Tuberculosis

Levofloxacin

Linezolid

Antibiotics

Bacteria

Genetics

Medicine

Biology

Microbiology

Pharmacology

Antimicrobial Agents and Chemotherapy

There is an urgent need for new, potent antituberculosis (anti-TB) drugs with novel mechanisms of action that can be included in new regimens to shorten the treatment period for TB. After screening a library of carbostyrils, we optimized 3,4-dihydrocarbostyril derivatives and identified OPC-167832 as having potent antituberculosis activity. The MICs of the compound for Mycobacterium tuberculosis ranged from 0.00024 to 0.002 μg/ml. It had bactericidal activity against both growing and intracellular bacilli, and the frequency of spontaneous resistance for M. tuberculosis H37Rv was less than 1.

OPC-167832, a Novel Carbostyril Derivative with Potent Antituberculosis Activity as a DprE1 Inhibitor