Synthesis of Triazole Derivatives of 9-Ethyl-9H-carbazole and Dibenzo[b,d]furan and Evaluation of Their Antimycobacterial and Immunomodulatory Activity

1,4-Disubstituted 1,2,3-triazole derivatives of 9-ethyl-9H-carbazole and dibenzo[b,d]furan were synthesized by the Huisgen's 1,3-dipolar cycloaddition reaction between azides and terminal alkynes. The synthesized derivatives 7d, 8a, 8b, 9e, and 10c exhibited good MIC values, especially against Mycobacterium smegmatis and these compounds were further evaluated for their immunomodulatory activity. Majority of the compounds exhibited no toxicity on splenocytes and macrophages and the compounds 8a and 8b are proved as induced proliferator. These compounds have shown decreased production of TNF-α from LPS stimulated RAW 264.7 cells and among all these compounds, 7d has shown significant inhibition of TNF-α production. Molecular docking studies into the active site of mycobacterial DprE1 enzyme helped to establish a structural basis for inhibition of Mycobacterium tuberculosis and understand the type of ligand-protein interactions governing the binding affinity.