title: Conjugates of ferrocene with biological compounds. Coordination to gold complexes and antitumoral properties.
abstract: Several bioconjugates of ferrocene with biological compounds such as aminoacid esters and related species have been prepared by reaction of chlorocarbonyl ferrocene with the corresponding amino acid ester (histidine methyl ester, tryptophan methyl ester, methionine methyl ester and lysine ethyl ester) or histamine or prolinamide in the presence of NEt(3). The reaction of the tryptophan or prolinamide ferrocene conjugates with [Au(acac)(PR(3))] (acac=acetylacetonate) results in the substitution of the proton of the cyclic NH groups by the fragment AuPR(3)(+) affording the complexes [Au(FcCO-tryptophan-OMe)(PR(3))] or [Au(FcCO-prolinamide)(PR(3))] (Fc=ferrocenyl group). The reaction of FcCO-Met-OMe with [Au(OTf)(PR(3))] (OTF=trifluoromethysulfonate) or [Au(C(6)F(5))(3)(OEt(2))] yields the gold(I) or gold(III) derivatives [Au(FcCO-Met-OMe)(PR(3))]OTf or [Au(C(6)F(5))(3)(FcCO-Met-OMe)], respectively. Cytotoxicity studies towards several cancer lines such as MCF-7, HeLa or NIE-115 have been performed. The ferrocene bioconjugates show no activity whereas the gold complexes exhibit antiproliferative effect. Preliminary studies of interaction of compounds with cells were carried out with the goal of increasing our knowledge on the mechanism of action of these potential drugs.
authors.affiliation: Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea (ISQCH), CSIC-Universidad de Zaragoza, Pedro Cerbuna 12, E-50009 Zaragoza, Spain. gimeno@unizar.es
authors.forename: M Concepción
authors.initials: MC
authors.lastname: Gimeno
authors.forename: Helen
authors.initials: H
authors.lastname: Goitia
authors.forename: Antonio
authors.initials: A
authors.lastname: Laguna
authors.forename: M Elvira
authors.initials: ME
authors.lastname: Luque
authors.forename: M Dolores
authors.initials: MD
authors.lastname: Villacampa
authors.forename: Catarina
authors.initials: C
authors.lastname: Sepúlveda
authors.forename: Margarida
authors.initials: M
authors.lastname: Meireles
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004952:Esters / Q000737:chemistry; D005296:Ferrous Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D006046:Gold / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D000075163:Metallocenes; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000596:Amino Acids; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D004952:Esters; D005296:Ferrous Compounds; D000075163:Metallocenes; D017382:Reactive Oxygen Species; D006046:Gold; C004998:ferrocene