title: Ru(II)-based complexes with N-(acyl)-N',N'-(disubstituted)thiourea ligands: Synthesis, characterization, BSA- and DNA-binding studies of new cytotoxic agents against lung and prostate tumour cells.
abstract: Four ruthenium(II)-based complexes with N-(acyl)-N',N'-(disubstituted)thiourea derivatives (Th) were obtained. The compounds, with the general formula trans-[Ru(PPh3)2(Th)(bipy)]PF6, interact with bovine serum albumin (BSA) and DNA. BSA-binding constants, which were in the range of 3.3-6.5×10(4) M(-1), and the thermodynamic parameters (ΔG, ΔH and ΔS), suggest spontaneous interactions with this protein by electrostatic forces due to the positive charge of the complexes. Also, binding constant by spectrophotometric DNA titration (Kb = 0.8-1.8×10(4) M(-1)) and viscosity studies indicate weak interactions between the complexes and DNA. Cytotoxicity assays against DU-145 (prostate cancer) and A549 (lung cancer) tumour cells revealed that the complexes are more active in tumour cells than in normal (L929) cells, and that they present high cytotoxicity (low IC50 values) compared with the reference metallodrug, cisplatin.
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos, UFSCar, Rodovia Washington Luís KM 235, CP 676, 13561-901, São Carlos, SP, Brazil. Electronic address: rodricorrea@ufscar.br.
authors.forename: Rodrigo S
authors.initials: RS
authors.lastname: Correa
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos, UFSCar, Rodovia Washington Luís KM 235, CP 676, 13561-901, São Carlos, SP, Brazil.
authors.forename: Katia M
authors.initials: KM
authors.lastname: de Oliveira
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos, UFSCar, Rodovia Washington Luís KM 235, CP 676, 13561-901, São Carlos, SP, Brazil.
authors.forename: Fábio G
authors.initials: FG
authors.lastname: Delolo
authors.affiliation: Laboratório de Síntesis Orgánica, Facultad de Química, Universidad de la Habana, Habana 10400, Cuba.
authors.forename: Anislay
authors.initials: A
authors.lastname: Alvarez
authors.affiliation: Laboratório de Síntesis Orgánica, Facultad de Química, Universidad de la Habana, Habana 10400, Cuba.
authors.forename: Raúl
authors.initials: R
authors.lastname: Mocelo
authors.affiliation: Laboratório de Síntesis Orgánica, Facultad de Química, Universidad de la Habana, Habana 10400, Cuba.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Plutin
authors.affiliation: Departamento de Gerontologia, Universidade Federal de São Carlos, São Carlos, SP, Brazil.
authors.forename: Marcia R
authors.initials: MR
authors.lastname: Cominetti
authors.affiliation: Departamento de Física e Informática, Instituto de Física de São Carlos, Universidade de São Paulo, CP 369, 13560-970, São Carlos, SP, Brazil.
authors.forename: Eduardo E
authors.initials: EE
authors.lastname: Castellano
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos, UFSCar, Rodovia Washington Luís KM 235, CP 676, 13561-901, São Carlos, SP, Brazil. Electronic address: daab@ufscar.br.
authors.forename: Alzir A
authors.initials: AA
authors.lastname: Batista
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D055664:Electrochemical Techniques; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D012428:Ruthenium / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013053:Spectrophotometry; D013890:Thiourea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D008024:Ligands; D012710:Serum Albumin, Bovine; D012428:Ruthenium; D004247:DNA; C427203:calf thymus DNA; D013890:Thiourea
keywords: Acylthiourea ligands; BSA binding; DNA binding; Lung cancer; Prostate cancer; Ruthenium/phosphine/diimine complexes