Design of novel iron compounds as potential therapeutic agents against tuberculosis |
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Authors: | M Belén Tarallo Antonio Monge Ronny R Ribeiro Roberto C Mercader Clarice QF Leite Dinorah Gambino |
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Institution: | a Cátedra de Química Inorgánica, Facultad de Química, Universidad de la República, Gral. Flores 2124, C. C. 1157, 11800 Montevideo, Uruguayb CIFA, Universidad de Navarra, Pamplona, Spainc Centro de Química Inorgánica (CEQUINOR/CONICET-UNLP), C.C. 962, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 1900 La Plata, Argentinad Instituto de Física de São Carlos, Universidade de São Paulo, C.P. 369, 13560, São Carlos, Brazile Departamento de Física, IFLP-CONICET, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CC. 67, 1900 La Plata, Argentinaf Faculdade de Ciencias Farmacêuticas, Unesp, C.P. 582, 14801-902 Araquara(SP), Brazil |
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Abstract: | In the search for new therapeutic tools against tuberculosis two novel iron complexes, Fe(L-H)3], with 3-aminoquinoxaline-2-carbonitrile N1,N4-dioxide derivatives (L) as ligands, were synthesized, characterized by a combination of techniques, and in vitro evaluated. Results were compared with those previously reported for two analogous iron complexes of other ligands of the same family of quinoxaline derivatives. In addition, the complexes were studied by cyclic voltammetry and EPR spectroscopy. Cyclic voltammograms of the iron compounds showed several cathodic processes which were attributed to the reduction of the metal center (Fe(III)/Fe(II)) and the coordinated ligand. EPR signals were characteristic of magnetically isolated high-spin Fe(III) in a rhombic environment and arise from transitions between mS = ± 1/2 (geff ~ 9) or mS = ± 3/2 (geff ~ 4.3) states. Mössbauer experiments showed hyperfine parameters that are typical of high-spin Fe(III) ions in a not too distorted environment. The novel complexes showed in vitro growth inhibitory activity on Mycobacterium tuberculosis H37Rv (ATCC 27294), together with very low unspecific cytotoxicity on eukaryotic cells (cultured murine cell line J774). Both complexes showed higher inhibitory effects on M. tuberculosis than the “second-line” therapeutic drugs. |
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Keywords: | Tuberculosis Iron Quinoxaline N1 N4-dioxides Mycobacterium tuberculosis |
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