8-nitrobenzothiazinones, such as BTZ043 and PBTZ169, inhibit decaprenylphosphoryl-beta-D-ribose 2' -oxidase (DprE1) and display nanomolar bactericidal activity against Mycobacterium tuberculosis in vitro. SAR studies revealed the 8-nitro group of the BTZ scaffold to be crucial for the mechanism of action, which involves formation of a semi-mercaptal bond with Cys387 in the active site of DprE1. To date, substitution of the 8-nitro group has led to extensive loss of antimycobacterial activity.
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