IN VITRO ANTIMYCOBACTERIAL ACTIVITY OF DIHYDROSPHINGOSINE ANALOGS AGAINST THE H37RA STRAIN OF MYCOBACTERIUM TUBERCULOSIS

Introduction/Objective: Tuberculosis (TB) remains one of the leading causes of death from infectious diseases worldwide, especially in high-burden countries such as Brazil. Despite the existence of effective therapeutic regimens, the prolonged treatment time and side effects contribute to poor adherence and favor the emergence of resistant strains. Identifying new compounds with innovative mechanisms of action is essential to overcome these limitations. Among the studied compounds, sphingolipids ‒ including dihydrosphingosine, one of their representatives ‒ have stood out for their ability to modulate the immune response and exert antimicrobial effects in infected macrophages. In this study, four novel synthetic dihydrosphingosine analogs were evaluated with the objective of investigating their in vitro antimycobacterial activity against the H37Ra strain of Mycobacterium tuberculosis. Methods: The compounds were synthesized and characterized at the University of Salamanca (Spain) and submitted to antimycobacterial analysis using the 96-well plate colorimetric microdilution method, as described by Palomino et al. (2002). The strain used was M. tuberculosis H37Ra (ATCC 25177), susceptible to all first-line drugs and classified as avirulent. Results: Compounds AFJ-6, AFJ-4, AFJ-7, and AFJ-9 presented minimum inhibitory concentration (MIC) values of 16, 32, 32, and 64 µg/mL, respectively, against the H37Ra strain. The results demonstrate initial antimycobacterial activity of the tested analogs, with emphasis on AFJ-6, which showed the lowest MIC. Although additional studies are needed, these findings reinforce the therapeutic potential of these molecules. Conclusion: The dihydrosphingosine analogs demonstrated the ability to inhibit growth of the H37Ra strain, representing an initial advance in the search for new therapeutic candidates against TB. These results justify continuation of investigations, including bacterial kill-curve assays, intracellular infection models, and cytotoxicity analyses, essential steps to validate the potential of these compounds as promising candidates for development of new anti-TB drugs.