Optimization and Evaluation of 5‐Styryl‐Oxathiazol‐2‐one Mycobacterium tuberculosis Proteasome Inhibitors as Potential Antitubercular Agents. Issue 3 (17th April 2015)

• Record Type: Journal Article
• Authors: Russo, Francesco; Gising, Johan; Åkerbladh, Linda; Roos, Annette K.; Naworyta, Agata; Mowbray, Sherry L.; Sokolowski, Anders; Henderson, Ian; Alling, Torey; Bailey, Mai A.; Files, Megan; Parish, Tanya; Karlén, Anders; Larhed, Mats
• Is Part Of: ChemistryOpen. Volume 4:Issue 3(2015:Jun.)
• Page Start: 342
• Page End: 362
• Publication Date: 2015-04-17
• Subjects: Chemistry -- Periodicals; 540; 540.5
• DOI: 10.1002/open.201500001
• Languages: English
• ISSNs: 2191-1363

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>This is the first report of 5‐styryl‐oxathiazol‐2‐ones as inhibitors of the <italic>Mycobacterium tuberculosis</italic> (<italic>Mtb</italic>) proteasome. As part of the study, the structure–activity relationship of oxathiazolones as <italic>Mtb</italic> proteasome inhibitors has been investigated. Furthermore, the prepared compounds displayed a good selectivity profile for <italic>Mtb</italic> compared to the human proteasome. The 5‐styryl‐oxathiazol‐2‐one inhibitors identified showed little activity against replicating <italic>Mtb</italic>, but were rapidly bactericidal against nonreplicating bacteria. (<italic>E</italic>)‐5‐(4‐Chlorostyryl)‐1, 3, 4‐oxathiazol‐2‐one) was most effective, reducing the colony‐forming units (CFU)/mL below the detection limit in only seven days at all concentrations tested. The results suggest that this new class of <italic>Mtb</italic> proteasome inhibitors has the potential to be further developed into novel antitubercular agents for synergistic combination therapies with existing drugs.</p> </abstract>