title: Coordination of nitro-thiosemicarbazones to ruthenium(II) as a strategy for anti-trypanosomal activity improvement.
abstract: Complexes [RuCl(H4NO(2)Fo4M)(bipy)(dppb)]PF(6) (1), [RuCl(H4NO(2)Fo4M)(Mebipy)(dppb)]PF(6) (2), [RuCl(H4NO(2)Fo4M)(phen)(dppb)]PF(6) (3), [RuCl(H4NO(2)Ac4M)(bipy)(dppb)]PF(6) (4), [RuCl(H4NO(2)Ac4M)(Mebipy)(dppb)]PF(6) (5) and [RuCl(H4NO(2)Ac4M)(phen)(dppb)]PF(6) (6) with N(4)-methyl-4-nitrobenzaldehyde thiosemicarbazone (H4NO(2)Fo4M) and N(4)-methyl-4-nitroacetophenone thiosemicarbazone (H4NO(2)Ac4M) were obtained from [RuCl(2)(bipy)(dppb)], [RuCl(2)(Mebipy)(dppb)], and [RuCl(2)(phen)(dppb)], (dppb = 1,4-bis(diphenylphospine)butane; bipy = 2,2'-bipyridine; Mebipy = 4,4'-dimethyl-2,2'-bipyridine; phen = 1,10-phenanthroline). In all cases the thiosemicarbazone is attached to the metal center through the sulfur atom. Complexes (1-6), together with the corresponding ligands and the Ru precursors were evaluated for their ability to in vitro suppress the growth of Trypanosoma cruzi. All complexes were more active than their corresponding ligands and precursors. Complexes (1-3) and (5) revealed to be the most active among all studied compounds with ID(50) = 0.6-0.8 microM. In all cases the association of the thiosemicarbazone with ruthenium, dppb and bipyridine or phenanthroline in one same complex proved to be an excellent strategy for activity improvement.
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos, 13565-905 São Carlos (SP), Brazil.
authors.forename: Claudia
authors.initials: C
authors.lastname: Rodrigues
authors.forename: Alzir A
authors.initials: AA
authors.lastname: Batista
authors.forename: Javier
authors.initials: J
authors.lastname: Ellena
authors.forename: Eduardo E
authors.initials: EE
authors.lastname: Castellano
authors.forename: Diego
authors.initials: D
authors.lastname: Benítez
authors.forename: Hugo
authors.initials: H
authors.lastname: Cerecetto
authors.forename: Mercedes
authors.initials: M
authors.lastname: González
authors.forename: Letícia R
authors.initials: LR
authors.lastname: Teixeira
authors.forename: Heloisa
authors.initials: H
authors.lastname: Beraldo
mesh_terms: D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D018360:Crystallography, X-Ray; D004563:Electrochemistry; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D012428:Ruthenium / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D013882:Thiosemicarbazones / Q000737:chemistry*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development
chemical_list: D000981:Antiprotozoal Agents; D009942:Organometallic Compounds; D013882:Thiosemicarbazones; D012428:Ruthenium