title: Ruthenium(II) phosphine/diimine/picolinate complexes: inorganic compounds as agents against tuberculosis.
abstract: This paper describes the synthesis and characterization of four new ruthenium complexes containing 1,4 bis(diphenylphosphino)butane (dppb), 2-pyridinecarboxylic acid anion (pic) and the diimines [(2,2'-bipyridine (bipy), 4,4'-dimethyl-2,2'-bipyridine (Me-bipy), 4,4'-dichloro-2,2'-bipyridine (Cl-bipy) and 1,10-phenanthroline (phen) as ligands, with formulae [Ru(pic)(dppb)(bipy)]PF(6) (SCAR01), [Ru(pic)(dppb)(Me-bipy)]PF(6) (SCAR02), [Ru(pic)(dppb)(Cl-bipy)]PF(6) (SCAR03) and [Ru(pic)(dppb)(phen)]PF(6) (SCAR04). Additionally, the in vitro anti-Mycobacterium tuberculosis (MTB) activity, cytotoxicity and activity against in vitro infection of these complexes and two more complexes, cis-[Ru(pic)(dppe)(2)]PF(6) (SCAR05) and cis-[RuCl(2)(dppb)(bipy)] (SCAR06), and their free ligands are described and discussed. All compounds showed excellent MIC against MTB, low cytotoxicity and a selectivity index higher than 10. Also, all compounds showed significant intracellular inhibition and the compound SCAR05 showed a better activity than rifampin and SQ109. This is the first report of activity against in vitro infection of ruthenium compounds.
authors.affiliation: Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, CEP 14801-902, Araraquara, SP, Brazil. pavanfer@yahoo.com.br
authors.forename: Fernando R
authors.initials: FR
authors.lastname: Pavan
authors.forename: Gustavo V
authors.initials: GV
authors.lastname: Poelhsitz
authors.forename: Marilia I F
authors.initials: MI
authors.lastname: Barbosa
authors.forename: Sergio R A
authors.initials: SR
authors.lastname: Leite
authors.forename: Alzir A
authors.initials: AA
authors.lastname: Batista
authors.forename: Javier
authors.initials: J
authors.lastname: Ellena
authors.forename: Leticia S
authors.initials: LS
authors.lastname: Sato
authors.forename: Scott G
authors.initials: SG
authors.lastname: Franzblau
authors.forename: Virtudes
authors.initials: V
authors.lastname: Moreno
authors.forename: Dinorah
authors.initials: D
authors.lastname: Gambino
authors.forename: Clarice Q F
authors.initials: CQ
authors.lastname: Leite
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D018360:Crystallography, X-Ray; D006801:Humans; D007097:Imines / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D009942:Organometallic Compounds / Q000494:pharmacology; D010720:Phosphines / Q000737:chemistry / Q000494:pharmacology*; D010848:Picolinic Acids / Q000737:chemistry / Q000494:pharmacology*; D012428:Ruthenium / Q000737:chemistry / Q000494:pharmacology*; D014376:Tuberculosis / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D007097:Imines; D009942:Organometallic Compounds; D010720:Phosphines; D010848:Picolinic Acids; D012428:Ruthenium; C044646:phosphine; C030614:picolinic acid