The antitubercular activity of various nitro(triazole/imidazole)-based compounds

Publication date: Available online 28 September 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Maria V. Papadopoulou, William D. Bloomer, Howard S. Rosenzweig
Twenty three 3-nitrotriazole- and five nitroimidazole-based compounds, mostly amides, were screened for antitubercular activity against Mycobacterium tuberculosis H37Rv (Mtb H37Rv) under aerobic or low oxygen conditions, intracellular activity in murine J774 macrophages or THP-1 cells, activity against resistant Mtb strains as well as cytotoxicity in normal cells. Compounds with a Minimum Inhibitory Concentration (MIC) less than 10 μM and 10-50 μM were characterized as active and moderately active, respectively, whereas compounds with a MIC > 50 μM were characterized inactive. Fifteen 3-nitrotriazole-based compounds were active or moderately active against aerobic Mtb and thirteen of them were bactericidal, however, only four 3-nitrotriazoles were moderately active against anaerobic Mtb. All examined 2-nitroimidazole-based compounds were inactive against aerobic Mtb, and from the ones examined against anaerobic Mtb, only one was found moderately active. All examined compounds demonstrated intracellular activity and lack of cross-resistance. The five active 3-nitrotriazoles demonstrated good selectivity for Mtb. In conclusion, these classes of 3-nitrotriazole-based compounds merit further investigation as potential antitubercular agents.

Graphical abstract

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