Sequential synthesis of amino-1,4-naphthoquinone-appended triazoles and triazole-chromene hybrids and their antimycobacterial evaluation

•We have synthesized a library of naphthoquinone-triazole hybrids by click reaction.•These targets accessed via three-component sequential manner using Et3N/CuI in water.•Aminonaphthoquinone-appended iminochromene-triazole hybrids were also synthesized.•Triazoles were screened in vitro activity against Mycobacterium tuberculosis H37Rv.•Among the triazoles, 7d has emerged as the most active one with IC50 = 1.87 μM.

A general method for the synthesis of a library of hitherto unreported amino-1,4-naphthoquinone-appended triazoles was accomplished via a sequential three-component reaction of substituted N-propargylaminonaphthoquinones with variously substituted alkyl bromides/2-bromonaphthalene-1,4-dione and sodium azide in the presence of Et3N/CuI in water. Aminonaphthoquinone-appended iminochromene-triazole hybrid heterocycles were also synthesized from the amino-1,4-naphthoquinone-appended-1,2,3-triazolylacetonitriles. All the triazole hybrids were screened for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB). Among the triazoles, 2-(((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)(4-(trifluoromethyl)phenyl)amino)naphthalene-1,4-dione (7d) emerged as the most active one with IC50 = 1.87 μM, being more potent than the anti-TB drugs, cycloserine (6 times), pyrimethamine (20 times) and equipotent as the drug ethambutol (IC50 < 1.56 μM).

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide