836-1Compounds of iron, cobalt, nickel and copper: an anti-tuberculosis and cytotoxicity activity.
Autores:Heloisa Barbosa de Barros (UNESP - Universidade Estadual Paulista) ; Fernando Rogério Pavan (UNESP - Universidade Estadual Paulista) ; Clarice Queico Fujimura Leite (UNESP - Universidade Estadual Paulista) ; Melinda Poggi (UDELAR - Universidad de la República Uruguay) ; Dinorah Gambino (UDELAR - Universidad de la República Uruguay) ; María H. Torre (UDELAR - Universidad de la República Uruguay)


Introduction: Mycobacterium tuberculosis ⟨MTB⟩ is the mainly agent of tuberculosis ⟨TB⟩ and responsible for the death of around three million people worldwide. The TB remains a big problem of public health and until now there is no effective manner to control it. Factors as length of the treatment, the rise of MDR and XDR ⟨multi-drug resistance and the extensive-drug resistance⟩ and the small therapeutic arsenal against the bacteria, promote the growth of this problem. Medicinal chemistry is taking a growing interest in the development of metal complexes for use as drugs. In this work was determined the Minimum Inhibitory Concentration ⟨MIC⟩ against MTB of three isoniazid ⟨INH⟩ metal complexes: ⟨Co⟨INH⟩2Cl⟨H2O⟩ ⟩Cl∙2.5H2O ⟨Co-INH⟩, ⟨Cu⟨INH⟩ ⟨H2O⟩2⟩SO4∙H2O ⟨Cu-INH⟩ and ⟨Ni⟨INH-1⟩ ⟨H2O⟩ 2⟩Cl∙0.5H2O ⟨Ni-INH⟩ and their cytotoxicity index ⟨IC50⟩ on J774A.1 macrophages. Materials and methods: First, the complexes were tested against MTB H37Rv, to determine the MIC ⟨defined as the lowest concentration resulting in 90% inhibition of growth of MTB⟩ performed by REMA ⟨Resazurin Microtiter Assay⟩ technique. The ⟨IC50⟩ ⟨defined as the highest drug concentration at which 50% of the cells are viable relative to the control⟩ on J774 macrophages lineage was determined through the methodology described by Pavan et al, 2010. In both trials, the results were observed by visual colorimetric change and fluorescence ⟨TECAN Spectrafluor ®⟩ in response to cell metabolism. The selectivity index ⟨SI⟩ was calculated by dividing IC50 by the MIC; if the SI is higher than 10, the compound is considered safe. Discussion of the results: All compounds tested showed MIC promising, and low cytotoxic values ⟨IC50⟩ qualifying them as activity against the bacteria and safe. The results obtained were: Ni-INH ⟨MIC: 0.195 μg⁄mL, IC50: 625 μg⁄mL, IS: 3205.13⟩, Co-INH ⟨MIC: 0.195 μg⁄mL, IC50: 625 μg⁄mL, IS: 3205.13⟩, Cu-INH ⟨MIC: 0.78 μg ⁄mL, IC50: 48.8 μg⁄mL, IS: 62.56⟩. Conclusion: The results presented above demonstrate that the compounds possess the first necessary characteristics to qualify as potential drugs against Mycobacterium tuberculosis Keywords: Mycobacterium tuberculosis;; IC50; REMA Financial support: CAPES and FAPESP ⟨proc.: 2009⁄06499-1 e 2011⁄11593-7⟩. The authors would like to thank CYTED network RIIDFCM 209RT0380.

Palavras-chave:  IC50, Mycobacterium tuberculosis, REMA