title: Antiparasitic activities of novel ruthenium/lapachol complexes.
abstract: The present study describes the synthesis, characterization, antileishmanial and antiplasmodial activities of novel diimine/(2,2'-bipyridine (bipy), 1,10-phenanthroline (phen), 4,4'-methylbipyridine (Me-bipy) and 4,4'-methoxybipyridine (MeO-bipy)/phosphine/ruthenium(II) complexes containing lapachol (Lap, 2-hydroxy-3-(3-33 methyl-2-buthenyl)-1,4-naphthoquinone) as bidentate ligand. The [Ru(Lap)(PPh3)2(bipy)]PF6 (1), [Ru(Lap)(PPh3)2(Me-bipy)]PF6 (2), [Ru(Lap)(PPh3)2(MeO-bipy)]PF6(3) and[Ru(Lap)(PPh3)2(phen)]PF6 (4) complexes, PPh3=triphenylphospine, were synthesized from the reactions of cis-[RuCl2(PPh3)2(X-bipy)] or cis-[RuCl2(PPh3)2(phen)], with lapachol. The [RuCl2(Lap)(dppb)] (5) [dppb=1,4-bis(diphenylphosphine)butane] was synthesized from the mer-[RuCl3(dppb)(H2O)] complex. The complexes were characterized by elemental analysis, molar conductivity, infrared and UV-vis spectroscopy, (31)P{(1)H} and (1)H NMR, and cyclic voltammetry. The Ru(III) complex, [RuCl2(Lap)(dppb)], was also characterized by the EPR technique. The structure of the complexes [Ru(Lap)(PPh3)2(bipy)]PF6 and [RuCl2(Lap)(dppb)] was elucidated by X-ray diffraction. The evaluation of the antiparasitic activities of the complexes against Leishmania amazonensis and Plasmodium falciparum demonstrated that lapachol-ruthenium complexes are more potent than the free lapachol. The [RuCl2(Lap)(dppb)] complex is the most potent and selective antiparasitic compound among the five new ruthenium complexes studied in this work, exhibiting an activity comparable to the reference drugs.
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos, CP 676, CEP 13565-905, São Carlos (SP), Brazil.
authors.forename: Marília I F
authors.initials: MI
authors.lastname: Barbosa
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos, CP 676, CEP 13565-905, São Carlos (SP), Brazil.
authors.forename: Rodrigo S
authors.initials: RS
authors.lastname: Corrêa
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos, CP 676, CEP 13565-905, São Carlos (SP), Brazil.
authors.forename: Katia Mara
authors.initials: KM
authors.lastname: de Oliveira
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos, CP 676, CEP 13565-905, São Carlos (SP), Brazil.
authors.forename: Claudia
authors.initials: C
authors.lastname: Rodrigues
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, CP 369, CEP 13560-970, São Carlos (SP), Brazil.
authors.forename: Javier
authors.initials: J
authors.lastname: Ellena
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, CP 369, CEP 13560-970, São Carlos (SP), Brazil.
authors.forename: Otaciro R
authors.initials: OR
authors.lastname: Nascimento
authors.affiliation: Laboratório de Engenharia Tecidual e Imunofarmacologia, Fiocruz, CEP: 40296-710, Salvador (BA), Brazil.
authors.forename: Vinícius P C
authors.initials: VP
authors.lastname: Rocha
authors.affiliation: Laboratório de Engenharia Tecidual e Imunofarmacologia, Fiocruz, CEP: 40296-710, Salvador (BA), Brazil.
authors.forename: Fabiana R
authors.initials: FR
authors.lastname: Nonato
authors.affiliation: Laboratório de Engenharia Tecidual e Imunofarmacologia, Fiocruz, CEP: 40296-710, Salvador (BA), Brazil.
authors.forename: Taís S
authors.initials: TS
authors.lastname: Macedo
authors.affiliation: Universidade Federal da Paraíba Laboratório de Tecnologia Farmacêutica, CEP 58051-900, João Pessoa (PB), Brazil.
authors.forename: José Maria
authors.initials: JM
authors.lastname: Barbosa-Filho
authors.affiliation: Laboratório de Engenharia Tecidual e Imunofarmacologia, Fiocruz, CEP: 40296-710, Salvador (BA), Brazil; Centro de Biotecnologia e Terapia Celular, Hospital São Rafael, CEP 41253-190, Salvador (BA), Brazil.
authors.forename: Milena B P
authors.initials: MB
authors.lastname: Soares
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos, CP 676, CEP 13565-905, São Carlos (SP), Brazil. Electronic address: daab@power.ufscar.br.
authors.forename: Alzir A
authors.initials: AA
authors.lastname: Batista
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical; D006801:Humans; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000187:drug effects; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D009285:Naphthoquinones / Q000737:chemistry; D010963:Plasmodium falciparum / Q000187:drug effects; D012428:Ruthenium / Q000737:chemistry*; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000962:Antimalarials; D056831:Coordination Complexes; D009285:Naphthoquinones; D014344:Trypanocidal Agents; D012428:Ruthenium; C008252:lapachol
keywords: Antileishmanial and antiplasmodial activities; Cytotoxicity; Ruthenium (II) and (III) lapachol complex