Tuberculosis (TB) is one of the leading cause of dead mainly produced by the infectious agent Mycobacterium tuberculosis. The most common form of TB affects the lungs. It is estimated that 10.8 million people are infected with TB worldwide. Especially HIV patients are more susceptible to contract TB. The current treatment for TB includes the use of special antibiotics, such as isoniazid, rifampicin, and pyrazinamide. However, to be effective, TB treatment must last from 4 to 6 months. Despite the availability of drugs for TB, the long treatment duration and potential side effects lead many patients to abandon treatment. Additionally, the emergence of drug-resistant strains of M. tuberculosis hinders TB treatment. N-containing heterocycles are privileged compounds with broad biological applications including antibacterial. Among them, triazines could serve as promising anti-TB agents. There exist three isomers of triazine compounds based on the position of nitrogen atoms in the ring, 1,2,3-triazine, 1,2,4-triazine and 1,3,5-triazine. However, 1,2,3-triazine is the least biologically explored isomer. Recently our group developed new methodologies to obtain 1,2,3-triazine 1-oxide compounds, 1,2,3-triazine and 3,6-dihydro-1,2,3-triazine 1-oxide derivatives with very high yields, and with a broad substrate scope. In this work, we hypothesized that 1,2,3-triazine derivatives could act as anti-Mycobacterium tuberculosis with low cytotoxicity. For that purpose, we assessed the antibacterial activity of 1,2,3-triazine 1-oxide, 1,2,3-triazine and 3,6-dihydro-1,2,3-triazine 1-oxide compounds against H37Rv Mycobacterium tuberculosis strain using Microplate Alama Blue Assay (MABA) to determined their Minimum Inhibitory Concentration values (MIC). In general, deoxygenated 1,2,3-triazines showed lower MIC values. We found that the compounds with the lowest MIC values from each series were 4c (MIC < 40 µM), 5e (MIC < 20 µM) and 6n (MIC < 30 µM). Further, we performed cytotoxic studies of the best three active compounds from each triazine series. Only compound 5c (MIC< 20 µM) had a SI > 10, which makes it safe and selective at needed concentration to exert its biocidal activity without affecting the selected healthy cell line. These results confirm that triazine compounds could act as promising candidates as anti-TB agents.

Scott Franzblau

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