Macozinone

Macozinone, also known as PBTZ169, is an experimental anti-tuberculosis drug belonging to the benzothiazinone class. It is an investigational antibiotic and has not been approved for clinical use.

Mechanism and use: Macozinone targets DprE1, an essential enzyme in the mycobacterial cell wall biosynthesis pathway. By inhibiting DprE1, the compound disrupts the production of arabinan, a key component of the cell wall, leading to impaired growth or death of Mycobacterium tuberculosis. The nitroaromatic benzothiazinone structure is central to its activity, and the drug has shown activity against M. tuberculosis strains in vitro, including some drug-resistant variants. In animal models, macozinone has demonstrated efficacy consistent with its proposed mechanism.

Development and status: Macozinone has undergone early-stage clinical testing to assess safety, tolerability, pharmacokinetics, and efficacy in tuberculosis. While results have illustrated the potential of the compound, development has faced challenges related to safety signals and regulatory considerations. As with other experimental TB therapies, macozinone had not obtained regulatory approval in major markets.

Chemistry and nomenclature: The compound is a nitro-containing benzothiazinone. Its development is part of the broader class of benzothiazinones (BTZs), which are investigated for their mechanism of inhibiting DprE1 in Mycobacterium tuberculosis. Synonyms commonly used include macozinone and PBTZ169.

See also: DprE1 inhibitors, BTZ043, tuberculosis drug development, benzothiazinones.