Identification of antitubercular benzothiazinone compounds by ligand-based design.
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.
Institute for Molecular Bioscience, University of Queensland, St. Lucia, Queensland 4072, Australia.
Tomislav
T
Karoli
Bernd
B
Becker
Johannes
J
Zuegg
Ute
U
Möllmann
Soumya
S
Ramu
Johnny X
JX
Huang
Matthew A
MA
Cooper
D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D008024:Ligands; D013843:Thiazines / Q000737:chemistry / Q000494:pharmacology*
D000995:Antitubercular Agents; D008024:Ligands; D013843:Thiazines