title: Chiral Platinum(II) Complexes Featuring Phosphine and Chloroquine Ligands as Cytotoxic and Monofunctional DNA-Binding Agents.
abstract: Chiral molecules in nature are involved in many biological events; their selectivity and specificity make them of great interest for understanding the behavior of bioactive molecules, by providing information about the chiral discrimination. Inspired by these conformational properties, we present the design and synthesis of novel chiral platinum(II) complexes featuring phosphine and chloroquine ligands with the general formula [PtCl(P)2(CQ)]PF6 (where (P)2 = triphenylphosphine (PPh3) (5), 1,3-bis(diphenylphosphine)propane (dppp) (6), 1,4-bis(diphenylphosphine)butane (dppb) (7), 1,1'-bis(diphenylphosphine)ferrocene (dppf) (8), and CQ = chloroquine] and their precursors of the type [PtCl2(P)2] are described. The complexes were characterized by elemental analysis, absorption spectroscopy in the infrared and ultraviolet-visible (UV-vis) regions, multinuclear ((1)H, (13)C, (31)P, (15)N, and (195)Pt) NMR spectroscopy, cyclic voltammetry, and mass spectrometry (in the case of chloroquine complexes). The interactions of the new platinum-chloroquine complexes with both albumin (BSA), using fluorescence spectroscopy, and DNA, by four widely reported methods were also evaluated. These experiments showed that these Pt-CQ complexes interact strongly with DNA and have high affinities for BSA, in contrast to CQ and CQDP (chloroquine diphosphate), which interact weakly with these biomolecules. Additional assays were performed in order to investigate the cytotoxicity of the platinum complexes against two healthy cell lines (mouse fibroblasts (L929) and the Chinese hamster lung (V79-4)) and four tumor cell lines (human breast (MDA-MB-231 and MCF-7), human lung (A549), and human prostate (DU-145)). The results suggest that the Pt-CQ complexes are generally more cytotoxic than the free CQ, showing that they are promising as anticancer drugs.
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos-UFSCar, CEP 13565-905, São Carlos-SP, Brazil.
authors.forename: Wilmer
authors.initials: W
authors.lastname: Villarreal
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos-UFSCar, CEP 13565-905, São Carlos-SP, Brazil.
authors.forename: Legna
authors.initials: L
authors.lastname: Colina-Vegas
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos-UFSCar, CEP 13565-905, São Carlos-SP, Brazil.
authors.forename: Clayton
authors.initials: C
authors.lastname: Rodrigues de Oliveira
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, CEP 13560-970, São Carlos-SP, Brazil.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Tenorio
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, CEP 13560-970, São Carlos-SP, Brazil.
authors.forename: Javier
authors.initials: J
authors.lastname: Ellena
authors.affiliation: Instituto de Química, Universidade Estadual de Campinas-UNICAMP, CEP 13083-970, Campinas-SP, Brazil.
authors.forename: Fábio C
authors.initials: FC
authors.lastname: Gozzo
authors.affiliation: Departamento de Gerontologia, Universidade Federal de São Carlos-UFSCar, CEP , 13565-905, São Carlos-SP, Brazil.
authors.forename: Marcia Regina
authors.initials: MR
authors.lastname: Cominetti
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos-UFSCar, CEP 13565-905, São Carlos-SP, Brazil.
authors.forename: Antonio G
authors.initials: AG
authors.lastname: Ferreira
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos-UFSCar, CEP 13565-905, São Carlos-SP, Brazil.
authors.forename: Marco Antonio Barbosa
authors.initials: MA
authors.lastname: Ferreira
authors.affiliation: Instituto Nacional de Metrologia, Qualidade e Tecnologia, INMETRO, CEP , 25250-020 Rio de Janeiro-RJ, Brazil.
authors.forename: Maribel
authors.initials: M
authors.lastname: Navarro
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos-UFSCar, CEP 13565-905, São Carlos-SP, Brazil.
authors.forename: Alzir A
authors.initials: AA
authors.lastname: Batista
mesh_terms: D045744:Cell Line, Tumor; D002738:Chloroquine / Q000737:chemistry*; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010720:Phosphines / Q000737:chemistry*; D010984:Platinum / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D008024:Ligands; D010720:Phosphines; D010984:Platinum; D002738:Chloroquine; D004247:DNA; C044646:phosphine