Mycobacterium Bactericide, TCA1

A cell-permeable benzothiazolylthiophene that exhibits bactericidal activity against mycobacteria, including M. smegmatis, M. bovis GCG, and M. tuberculosis (MIC₅₀ = 30, 40, and 10 ng/mL, respectively, in biofilm medium; MIC₅₀ = 4.5, 3, 0.19 µg/mL, respectively, in 7H9 medium), but not E. coli, Staphylococcus aureus, or Pseudomonas aeruginosa, by simultaneously targeting DprE1 FAD-binding domain of DprE1/DprE2 required for Mycobacterium cell wall arabinan biosynthesis and the Mtb MoeW protein involved in the biosynthesis of MoCo, molybdenum cofactor indispensable for nitrate assimilation via MoCo-dependent enzymes. Either alone or used in combination, TCA1 is shown to greatly complement INH (Isoniazid) and RIF (Rifampicin) against both wt and drug-resistant Mtb cultures in vitro (1-7.5 µg/mL) and in treating acute and chronic Mtb H37Rv infections in mice in vivo (10-100 mg/kg p.o.) with no apparent host toxicity.

Cell permeable: yes

Primary Target
DprE1

Secondary Target
MoeW

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Wang, F., et al. 2013. Proc. Natl. Acad. Sci. USA110, E2510.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Toxicity: Standard Handling (A)