Rational design and synthesis of novel dibenzo[b,d]furan-1,2,3-triazole conjugates as potent inhibitors of Mycobacterium tuberculosis

•A series of novel dibenzofuran-1,2,3-triazole conjugates were synthesized via click chemistry.•All the new analogues were evaluated for their in vitro antimycobacterial activity.•Three derivatives 5a, 5d and 5f were resulted as best active antitubercular agents with selectivity index >25.•Dibenzofuran–triazole conjugates were emerged as lead antitubercular agents for optimization.

A series of novel dibenzo[b,d]furan-1,2,3-triazole conjugates, rationally designed by reorientation of dibenzo[b,d]furan pharmacophore and alkyl/aryl groups appended on 1,2,3-triazole core, were synthesized using click chemistry. The required key intermediate, 2-ethynyl dibenzo[b,d]furan 3 was prepared from dibenzofuran-2-carboxaldehyde using Corey–Fuchs reaction. Further reaction of 3 with various alkyl/aryl azides in the presence of copper catalyst produced 1,2,3-triazole conjugates in excellent yields. Evaluation of all the new compounds for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (ATCC27294), resulted 5a (MIC: 1.56 μg/mL), 5d (MIC: 0.78 μg/mL) and 5f (MIC: 0.78 μg/mL) as promising lead analogues. Among these three compounds, 1-(4-bromobenzyl)-4-(dibenzo[b,d]furan-2-yl)-1H-1,2,3-triazole (5f) emerged as the most promising antitubercular agent with lowest cytotoxicity (selectivity index: ≫25) against the HEK-293T cell line.

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