Identification of antitubercular benzothiazinone compounds by ligand-based design.
Karoli T, Becker B, Zuegg J, Möllmann U, Ramu S, Huang JX, Cooper MA.
1,3-Benzothiazin-4-ones (BTZs) are a novel class of TB drug candidates with potent activity against M. tuberculosis. An in silico ligand-based model based on structure-activity data from 170 BTZ compounds was used to design a new series. Compounds were tested against a panel of mycobacterial strains and were profiled for cytotoxicity, stability, and antiproliferative effects. Several of the compounds showed improved activity against MDR-TB while retaining low toxicity with higher microsomal, metabolic, and plasma stability.