Avaliação in vitro de derivados 1,2-alcanodiamina frente ao Mycobacterium tuberculosis sensível e multidroga resistente

Abstract

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), an infectious-contagious disease, considered one of the deadliest in the world. TB remains a major global public health problem and so far, there has been no effective way to eradicate it. A major change in TB trajectory occurred with the introduction of the first anti-TB drugs and consequently the emergence of resistance forms to antimycobacteria, resistant multidrug tuberculosis (MDR-TB) and extensively resistant tuberculosis (XDR-TB). From this, the need arises for new drugs to be proposed in the treatment of this disease. The present study aims to evaluate diamine derivatives, related to ethambutol, against sensitive Mtb and MDR. Ten compounds derived from the class 1,2-alkanediamine were synthesized and characterized structurally by the pharmaceutical chemistry laboratories of the University of Salamanca and provided through international cooperation. For the biological tests, the standard reference strain H37Rv (ATCC 27294) was classified as a strain sensitive to all drugs used to treat TB and a clinical isolate of a patient affected by pulmonary tuberculosis with a MDR profile, provided by the Health Laboratory Public of Pernambuco. Minimum Inhibitory Concentration (MIC) determined the evaluation of compound activity in 96-well plates by the colorimetric microdilution method. For cytotoxicity (CC50) the MTT test (3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide) was used with the J774A.1 cell line. The selectivity index (IS) was calculated by the ratio of MIC and CC50. The ten compounds tested had a MIC ranging from 4.0 to> 64.0 μM for strain H37Rv and MDR. With respect to CC50, the compounds had a concentration range ranging from 3.9 to 32.8 μM. Compound D15 exerted the best activity against the reference strain (H37Rv) and MDR strain (MDR 1576), however in the cytotoxicity test the compound that presented the best result was D10. Regarding the selectivity index, compounds A4 and A5 were the ones that obtained the best results even though they were below the ideal index. The compounds evaluated in this study showed moderate activity against Mtb and support the continuity of the study of 1,2-alkanediamine derivatives.