Design, synthesis and evaluation of antitubercular activity of Triclosan analogues

Abstract

Novel Triclosan mimic diphenyl ether derivatives 4a–k were designed and synthesized with lipophilicity considerably lesser than that of Triclosan. The binding mode of the compounds at the active site of enoyl-ACP reductase was analysed using docking method. The syntheses were carried out with one-pot reductive amination reaction and were characterized by spectral techniques. The synthesized compounds were evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv strain by Microplate Alamar Blue assay. Compounds 4h and 4j were the most active compounds with MIC equal to 25 μg/mL against M. tuberculosis H37Rv strain. All compounds were also examined for their cytotoxic potential against VERO and HepG2 cell lines and were safe even at 300 μg/mL. LogP of all the synthesized compounds was evaluated by RPHPLC and was significantly lesser than Triclosan. Keywords: Triclosan analogues, Enoyl-ACP reductase, Diphenyl ether derivatives, Lipophilicity, Antitubercular activity, LogP