title: Bioactivity of pyridine-2-thiolato-1-oxide metal complexes: Bi(III), Fe(III) and Ga(III) complexes as potent anti-Mycobacterium tuberculosis prospective agents.
abstract: In the search for new therapeutic tools against tuberculosis and to further address the therapeutic potential of pyridine-2-thiol 1-oxide (Hmpo) metal complexes, two new octahedral [M(III)(mpo)3] complexes, with M = Ga or Bi, were synthesized and characterized in the solid state and in solution. Attempts to crystallize [Ga(III)(mpo)3] in CH2Cl2 led to single crystals of the reaction product [GaCl(mpo)2], where the gallium(III) ion is in a square basis pyramidal environment, trans-coordinated at the basis to two pyridine-2-thiolato 1-oxide anions acting as bidentate ligands through their oxygen and sulfur atoms. The biological activity of the new [M(III)(mpo)3] complexes together with that of the previously reported Fe(III) analogous compound and the pyridine-2-thiol 1-oxide sodium salt (Na mpo) was evaluated on Mycobacterium tuberculosis. The compounds showed excellent activity, both in the standard strain H37Rv ATCC 27294 (pan-susceptible) and in five clinical isolates that are resistant to the standard first-line anti-tuberculosis drugs isoniazid and rifampicin. These pyridine-2-thiol 1-oxide derivatives are promising compounds for the treatment of resistant tuberculosis.
authors.affiliation: Cátedra de Química Inorgánica, Departamento Estrella Campos, Facultad de Química, Universidad de la República, Gral. Flores 2124, 11800 Montevideo, Uruguay.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Machado
authors.affiliation: Facultade de Ciencias Farmacêuticas, UNESP, 14801-902 Araraquara, SP, Brazil.
authors.forename: Leonardo Biancolino
authors.initials: LB
authors.lastname: Marino
authors.affiliation: Cátedra de Química Inorgánica, Departamento Estrella Campos, Facultad de Química, Universidad de la República, Gral. Flores 2124, 11800 Montevideo, Uruguay.
authors.forename: Bruno
authors.initials: B
authors.lastname: Demoro
authors.affiliation: Departamento de Física, Facultad de Ciencias Exactas, Universidad Nacional de La Plata and IFLP (CONICET, CCT-La Plata), C.C. 67, 1900 La Plata, Argentina.
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Echeverría
authors.affiliation: Departamento de Física, Facultad de Ciencias Exactas, Universidad Nacional de La Plata and IFLP (CONICET, CCT-La Plata), C.C. 67, 1900 La Plata, Argentina.
authors.forename: Oscar E
authors.initials: OE
authors.lastname: Piro
authors.affiliation: Facultade de Ciencias Farmacêuticas, UNESP, 14801-902 Araraquara, SP, Brazil.
authors.forename: Clarice Q F
authors.initials: CQ
authors.lastname: Leite
authors.affiliation: Facultade de Ciencias Farmacêuticas, UNESP, 14801-902 Araraquara, SP, Brazil.
authors.forename: Fernando R
authors.initials: FR
authors.lastname: Pavan
authors.affiliation: Cátedra de Química Inorgánica, Departamento Estrella Campos, Facultad de Química, Universidad de la República, Gral. Flores 2124, 11800 Montevideo, Uruguay. Electronic address: dgambino@fq.edu.uy.
authors.forename: Dinorah
authors.initials: D
authors.lastname: Gambino
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D001729:Bismuth / Q000737:chemistry; D002522:Chlorocebus aethiops; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D018360:Crystallography, X-Ray; D005708:Gallium / Q000737:chemistry; D007501:Iron / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D014709:Vero Cells
chemical_list: D000900:Anti-Bacterial Agents; D056831:Coordination Complexes; D005708:Gallium; D007501:Iron; D001729:Bismuth
keywords: Bismuth(III); Gallium(III); Iron(III); Mycobacterium tuberculosis; Pyridine-2-thiol 1-oxide compounds