Sulfur rich 2-mercaptobenzothiazole and 1,2,3-triazole conjugates as novel antitubercular agents

• A series of benzfused heterocyclic derivatives have been synthesized.
• The compounds were evaluated for their antitubercular activity.
• Some of the compounds inhibited the growth of the Mycobacterium tuberculosis H37Rv at 8 μg/mL.
• Compounds 8b, 8f, 8g and 8l have been further identified as bactericidal.
• Molecular docking studies with DprE1 reveal the non covalent interactions.

A series of benzfused heterocyclic derivatives such as amide conjugates of 2-(benzo[d]thiazol-2-ylthio)acetic acid with aromatic/aliphatic/cyclic secondary amines (5a–5o & 8a–8m); 1,2,3-triazole conjugates of 2-mercaptobenzothiazoles and amide conjugates of indole-3-glyoxalic acid with cyclic secondary amines (14a–14g) have been synthesized and were screened for their antitubercular activity against Mycobacterium tuberculosis H37Rv strain by broth microdilution assay method. Compounds 8b, 8f, 8g and 8l inhibited the growth of the H37Rv strain at concentrations of 8 μg/mL. These compounds (8b, 8f, 8g and 8l) have been further identified as bactericidal and are completely killing the microbes at 32–64 μg/mL concentrations. Molecular docking studies of the active compounds reveal that these compounds are targeting DprE1 and may act as DprE1 inhibitors.

Sulfur rich 2-mercapto benzothiazole and 1,2,3-triazole conjugates demonstrated a potent antitubercular activity against Mycobacterium tuberculosis H37Rv strain and have been further identified as mycobactericidal.Figure optionsDownload as PowerPoint slide