2. Academic Validation
  3. Syntheses and Antituberculosis Activity of 1,3-Benzothiazinone Sulfoxide and Sulfone Derived from BTZ043

Syntheses and Antituberculosis Activity of 1,3-Benzothiazinone Sulfoxide and Sulfone Derived from BTZ043

  • ACS Med Chem Lett. 2014 Nov 29;6(2):128-33. doi: 10.1021/ml5003458.
Rohit Tiwari 1,  Patricia A Miller 1,  Sanghyun Cho 2,  Scott G Franzblau 2,  Marvin J Miller 1
Affiliations

Affiliations

  • 1 Department of Chemistry and Biochemistry, University of Notre Dame , Notre Dame, Indiana 46556, United States.
  • 2 Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago , 833 South Wood Street, Chicago, Illinois 60612, United States.
PMID: 25699139 DOI: 10.1021/ml5003458
Abstract

The discovery of 1,3-benzothiazin-4-ones (BTZs), especially BTZ043 and PBTZ-169 as potent agents for the treatment of tuberculosis, prompted intensive research related to development of potential antituberculosis agents based on electron deficient nitroaromatic scaffolds. Herein we report the syntheses, computational and NMR studies and anti-TB activity of oxidation products, 1,3-benzothiazinone sulfoxide (BTZ-SO) and 1,3-benzothiazinone sulfone (BTZ-SO2) derived from BTZ043. The combined computational and NMR work revealed differences in the total charge densities and molecular shapes of the oxidation products. While docking studies still suggested similar interactions and binding patterns for both products with the target DprE1 Enzyme, antituberculosis assays indicated remarkable differences in their activity. Interestingly, BTZ-SO possesses potent activity against nonpathogenic and pathogenic mycobacterial strains, but BTZ-SO2 is only weakly active.

Keywords

BTZ043; DprE1; oxidation; sulfone; sulfoxide; tuberculosis.

Figures