Sulfur-containing heterocycles have been widely exploited as antituberculosis agents . Researches from AstraZeneca® (AstraZeneca R&D, Bangalore, India) have discovered a diarylthiazole derivative after molecular optimizations in a previously identified hit. Compound (31) (Figure 11) showed potent antituberculosis activity with MIC90 values below 1.68 μM against several MDR-TB clinical isolates. In vitro drug metabolism and pharmacokinetics parameters were assessed for compound (31), which exhibited solubility of 31 μM, mouse plasma protein binding of 17% and mouse clearance of 170.4 μL/min/mg. Moreover, the authors have characterized the PrrBA as the molecular target of this derivative . PrrBA is a two-component system composed of the PrrB histidine kinase and PrrA response regulator and it plays an important role in mycobacterial virulence and metabolic adaptation to stress . In another work, Luoting Yu and coworkers reported a benzothiazinethione derivative as a potent antitubercular agent . Compound (32) (Figure 11), an analog of the drug candidate BTZ043 , presented MIC90 values below 0.03 μM against several MDR and XDR-TB clinical isolates. The pharmacokinetics in rats of this compound showed Cmax of 193 ng/mL, T1/2 of 1.45 h and 44.4% of absolute oral bioavailability. Furthermore, compound (32) demonstrated in vivo efficacy in a mice model, which was able to reduce the Mtb burden in lungs by 3.4 logs CFU . Thiazole and its analogue benzothiazole are also important sulfur-containing heterocycles with antituberculosis activity. For instance, the synthesis of a series of thirty-four thiazole derivatives have been reported and their antitubercular activity was assessed against several single drug-resistant strains. Compound (33) (Figure 11) showed MIC90 values ranging from 7.1 and 12.0 μM . Ramachandran and coworkers at AstraZeneca® (AstraZeneca R&D, Bangalore, India) also reported benzothiazoles derivatives as antitubercular. They discovered compound (34) (Figure 11) as a promising antituberculosis agent with MIC90 values below 4.62 μM against several single drug-resistant isolates. DprE1 was characterized as the target of compound (34). In addition, this compound demonstrated safety profile with low cytotoxicity against human A549 cell line (IC50 > 100 μM), negative Ames assay and moderate CYP isoform inhibition .