title: Ru(II)/clotrimazole/diphenylphosphine/bipyridine complexes: Interaction with DNA, BSA and biological potential against tumor cell lines and Mycobacterium tuberculosis.
abstract: Three ruthenium complexes [RuCl(CTZ)(bipy)(P-P)]PF6[P-P=1,2-bis(diphenylphosphino)ethane (dppe-1), 1,4-bis(diphenylphosphino)butane (dppb-2) and 1,1'-bis(diphenylphosphino)ferrocene (dppf-3), bipy=2,2'-bipiridine and clotrimazole (CTZ) 1-[(2-chlorophenyl)diphenylmethyl]-1H-imidazole] were synthesized. These complexes were characterized by a combination of elemental analysis, molar conductivity, infrared and UV-vis spectroscopy,1H,13C{1H} and31P{1H} nuclear magnetic resonance techniques, cyclic voltammetry and mass spectroscopy. Bovine serum albumin binding constants, which were in the range of 1.30-36.00×104M-1, and thermodynamic parameters suggest spontaneous interactions with this protein by electrostatic forces due to the positive charge of the complexes. DNA interactions studied by spectroscopic titration, viscosity measurements, gel electrophoresis, circular dichroism, ethidium bromide displacement and reactions with guanosine and guanosine monophosphate indicated the DNA binding affinity primarily through non-covalent interactions. All complexes 1-3 were tested against the human carcinoma cell lines MCF-7 (breast), A549 (lung) and DU-145 (prostate) presenting promising IC50values, between 0.50 and 14.00μM, in some cases lower than the IC50for the reference drug (cisplatin). The antimicrobial activity assays of the complexes provided evidence that they are potential agents against mycobacterial infections, specifically against Mycobacterium tuberculosis H37Rv.
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos-SP, CEP 13565-905, Brazil. Electronic address: esleg_24@hotmail.com.
authors.forename: Legna
authors.initials: L
authors.lastname: Colina-Vegas
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos-SP, CEP 13565-905, Brazil.
authors.forename: Jocely Lucena
authors.initials: JL
authors.lastname: Dutra
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos-SP, CEP 13565-905, Brazil.
authors.forename: Wilmer
authors.initials: W
authors.lastname: Villarreal
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos-SP, CEP 13565-905, Brazil.
authors.forename: João Honorato
authors.initials: JH
authors.lastname: de A Neto
authors.affiliation: Departamento de Gerontologia, Universidade Federal de São Carlos-SP, CEP 13565-905, Brazil.
authors.forename: Marcia Regina
authors.initials: MR
authors.lastname: Cominetti
authors.affiliation: Departamento de Ciências Biológicas, Faculdade de Ciências Farmacêuticas, UNESP, CEP 14800-900 Araraquara, SP, Brazil.
authors.forename: Fernando
authors.initials: F
authors.lastname: Pavan
authors.affiliation: Directoria de Metrologia Aplicada a Ciências da Vida, Instituto Nacional de Metrologia, Qualidade e Tecnologia, INMETRO, RJ, Brazil.
authors.forename: Maribel
authors.initials: M
authors.lastname: Navarro
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos-SP, CEP 13565-905, Brazil. Electronic address: daab@ufscar.br.
authors.forename: Alzir A
authors.initials: AA
authors.lastname: Batista
mesh_terms: D015082:2,2'-Dipyridyl / Q000737:chemistry*; D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002417:Cattle; D045744:Cell Line, Tumor; D003022:Clotrimazole / Q000737:chemistry*; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000494:pharmacology; D004247:DNA / Q000737:chemistry; D004996:Ethidium / Q000737:chemistry; D005296:Ferrous Compounds / Q000737:chemistry; D006157:Guanosine Monophosphate / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D000075163:Metallocenes; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000254:growth & development; D010720:Phosphines / Q000737:chemistry; D012428:Ruthenium / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000737:chemistry; D055672:Static Electricity; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014783:Viscosity
chemical_list: D000970:Antineoplastic Agents; D000995:Antitubercular Agents; D056831:Coordination Complexes; D005296:Ferrous Compounds; D000075163:Metallocenes; D010720:Phosphines; D012710:Serum Albumin, Bovine; D015082:2,2'-Dipyridyl; D012428:Ruthenium; D006157:Guanosine Monophosphate; D004247:DNA; C427203:calf thymus DNA; D004996:Ethidium; D003022:Clotrimazole; C519379:1,1'-bis(diphenylphosphino)ferrocene
keywords: Antitumor and anti-Mycobacterium tuberculosis; Clotrimazole; Ruthenium-bisdiphenylphosphine