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A High-throughput Compatible Assay to Evaluate Drug Efficacy against Macrophage Passaged Mycobacterium tuberculosis
Published on: March 24, 2017
Identification of Better Pharmacokinetic Benzothiazinone Derivatives as New Antitubercular Agents
Kai Lv1, Xuefu You1, Bin Wang2
1Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Abstract:
A series of new 8-nitro-6-(trifluoromethyl)-1,3-benzothiazin-4-one(BTZ) derivatives containing a C-2 nitrogen spiro-heterocycle moiety based on the structures of BTZ candidates BTZ043 and PBTZ169 were designed and synthesized as new antitubercular agents. Many of them were found to have excellent in vitro activity (MIC < 0.15 μM) against the drug susceptive Mycobacterium tuberculosis H37Rv strain and two clinically isolated multidrug-resistant strains. Compounds 11l and 11m display acceptable safety, greater aqueous solubility, and better pharmacokinetic profiles than PBTZ169, suggesting their promising potential to be lead compounds for future antitubercular drug discovery.
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