Compounds > 2-pyridin-2-yl-4h-1-3-benzothiazin-4-one

2-pyridin-2-yl-4h-1-3-benzothiazin-4-one and Tuberculosis

2-pyridin-2-yl-4h-1-3-benzothiazin-4-one has been researched along with Tuberculosis* in 1 studies

Other Studies

1 other study(ies) available for 2-pyridin-2-yl-4h-1-3-benzothiazin-4-one and Tuberculosis

Article	Year
The 8-Pyrrole-Benzothiazinones Are Noncovalent Inhibitors of DprE1 from Mycobacterium tuberculosis. Antimicrobial agents and chemotherapy, 2015, Volume: 59, Issue:8 8-Nitro-benzothiazinones (BTZs), such as BTZ043 and PBTZ169, inhibit decaprenylphosphoryl-β-d-ribose 2'-oxidase (DprE1) and display nanomolar bactericidal activity against Mycobacterium tuberculosis in vitro. Structure-activity relationship (SAR) studies revealed the 8-nitro group of the BTZ scaffold to be crucial for the mechanism of action, which involves formation of a semimercaptal 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. Here, we report the synthesis and characterization of the pyrrole-benzothiazinones PyrBTZ01 and PyrBTZ02, non-nitro-benzothiazinones that retain significant antimycobacterial activity, with MICs of 0.16 μg/ml against M. tuberculosis. These compounds inhibit DprE1 with 50% inhibitory concentration (IC50) values of <8 μM and present favorable in vitro absorption-distribution-metabolism-excretion/toxicity (ADME/T) and in vivo pharmacokinetic profiles. The most promising compound, PyrBTZ01, did not show efficacy in a mouse model of acute tuberculosis, suggesting that BTZ-mediated killing through DprE1 inhibition requires a combination of both covalent bond formation and compound potency. Topics: Alcohol Oxidoreductases; Animals; Antitubercular Agents; Bacterial Proteins; Catalytic Domain; Disease Models, Animal; Hep G2 Cells; Humans; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Piperazines; Pyridines; Pyrroles; Spiro Compounds; Structure-Activity Relationship; Thiazines; Tuberculosis	2015

Article

Year

The 8-Pyrrole-Benzothiazinones Are Noncovalent Inhibitors of DprE1 from Mycobacterium tuberculosis.

Antimicrobial agents and chemotherapy, 2015, Volume: 59, Issue:8

8-Nitro-benzothiazinones (BTZs), such as BTZ043 and PBTZ169, inhibit decaprenylphosphoryl-β-d-ribose 2'-oxidase (DprE1) and display nanomolar bactericidal activity against Mycobacterium tuberculosis in vitro. Structure-activity relationship (SAR) studies revealed the 8-nitro group of the BTZ scaffold to be crucial for the mechanism of action, which involves formation of a semimercaptal 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. Here, we report the synthesis and characterization of the pyrrole-benzothiazinones PyrBTZ01 and PyrBTZ02, non-nitro-benzothiazinones that retain significant antimycobacterial activity, with MICs of 0.16 μg/ml against M. tuberculosis. These compounds inhibit DprE1 with 50% inhibitory concentration (IC50) values of <8 μM and present favorable in vitro absorption-distribution-metabolism-excretion/toxicity (ADME/T) and in vivo pharmacokinetic profiles. The most promising compound, PyrBTZ01, did not show efficacy in a mouse model of acute tuberculosis, suggesting that BTZ-mediated killing through DprE1 inhibition requires a combination of both covalent bond formation and compound potency.

Topics: Alcohol Oxidoreductases; Animals; Antitubercular Agents; Bacterial Proteins; Catalytic Domain; Disease Models, Animal; Hep G2 Cells; Humans; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Piperazines; Pyridines; Pyrroles; Spiro Compounds; Structure-Activity Relationship; Thiazines; Tuberculosis

2015