The most important Mycobacterium genus is M. tuberculosis (MTB), the causative agent of tuberculosis. According to WHO data tuberculosis kills 3 million people each year and the global epidemic is growing and becoming more dangerous. It is a consequence of multi-drug resistance, and the phenomenon of HIV-TB co-infection. We have evaluated anti-TB activity of “functional carb-pharmacophores” (FCP) used as a new approach to compose functionalized sugar derivatives that have therapeutic potential (Witczak et al.) [1]. The initial collection applied for this study consists of 13 functionalized sugar derivatives including thio-sugar, anhydrosugar, sulfamidosugar and 1-4-S-thiodisacharide motifs. Our preliminary data suggest that thio-sugars (compounds 6-8) with 1-4-S-thio-linkage display significant antitubercular properties. The growth of Mycobacterium tuberculosis was completely inhibited by the presence of T6 (100 µM), T7 (1000 µM), T8 (350 µM) and inhibited in 50% (MIC50) by the presence of T6 (50 µM), T7 (500 µM), T8 (200 µM). The broth microdilution assay was used to identify the minimal inhibitory concentration (MIC) of the same compounds for Staphylococcus aureus (gram positive), E.coli (gram negative), Mycobacterium smegmatis (fast growing mycobacterium). All compounds appeared to only partially inhibit (20-30%) the growth of M. smegmatis in concentrations 1,25 – 5 mM. The growth of E. coli was partially (40%) inhibited in the presence of 5 mM of T6 and was not affected by the presence of as much as 10 mM of T7 and T8. On the other hand T7 and T8 in relatively high concentration (10 mM) were able to partially (20-40%) inhibit growth of S. aureus. We conclude that 1-4-thio-linked sugars are able to inhibit the growth of tubercle bacilli not affecting other bacteria and might be considered as highly-specific inhibitors of growth of M. tuberculosis. 1. Z. J. Witczak, T. Poplawski A. Czubatka, J. Sarnik, P. Tokarz, A. L. VanWert, R. Bielski, Bioorganic & Med. Chem. Lett., 2014, 24, 1752-1757. Acknowledgment: The study was supported by grant of Polish National Center of Science UMO 2014/15/B/NZ7/01002.

Evaluation of functional carb-pharmacophores as a potential inhibitors of Tubercle bacilli

251st National Meeting (2016)

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