title: Group 11 complexes with amino acid derivatives: Synthesis and antitumoral studies.
abstract: Gold(I), gold(III), silver(I) and copper(I) complexes with modified amino acid esters and phosphine ligands have been prepared in order to test their cytotoxic activity. Two different phosphine fragments, PPh3 and PPh2py (py=pyridine), have been used. The amino acid esters have been modified by introducing an aromatic amine as pyridine that coordinates metal fragments through the nitrogen atom, giving complexes of the type [M(L)(PR3)](+) or [AuCl3(L)] (L=l-valine-N-(4-pyridylcarbonyl) methyl ester (L1), l-alanine-N-(4-pyridylcarbonyl) methyl ester (L2), l-phenylalanine-N-(4-pyridylcarbonyl) methyl-ester) (L3); M=Au(I), Ag(I), Cu(I), PR3=PPh3, PPh2py). The in vitro cytotoxic activity of metal complexes was tested against four tumor human cell lines and one tumor mouse cell line. A metabolic activity test (3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide, MTT) was used and IC50 values were compared with those obtained for cisplatin. Several complexes displayed significant cytotoxic activities. In order to determine whether antiproliferation and cell death are associated with apoptosis, NIH-3T3 cells were exposed to five selected complexes (Annexin V+ FITC, PI) and analyzed by flow cytometry. These experiments showed that the mechanism by which the complexes inhibit cell proliferation inducing cell death in NIH-3T3 cells is mainly apoptotic.
authors.affiliation: Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea (ISQCH), CSIC-Universidad de Zaragoza, E-50009 Zaragoza, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Ortego
authors.affiliation: Universidade de Lisboa, Faculdade de Ciências, Departamento de Química e Bioquímica e Centro de Química e Bioquímica, Campo Grande, 1749-016, Lisboa, Portugal.
authors.forename: Margarida
authors.initials: M
authors.lastname: Meireles
authors.affiliation: Department of Biotechnology, Institute for Applied Microbiology, University of Material Resource and Life Science, Muthgasse 18, 1180, Vienna, Austria.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Kasper
authors.affiliation: Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea (ISQCH), CSIC-Universidad de Zaragoza, E-50009 Zaragoza, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Laguna
authors.affiliation: Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea (ISQCH), CSIC-Universidad de Zaragoza, E-50009 Zaragoza, Spain. Electronic address: dvilla@unizar.es.
authors.forename: M Dolores
authors.initials: MD
authors.lastname: Villacampa
authors.affiliation: Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea (ISQCH), CSIC-Universidad de Zaragoza, E-50009 Zaragoza, Spain. Electronic address: gimeno@unizar.es.
authors.forename: M Concepción
authors.initials: MC
authors.lastname: Gimeno
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000596:Amino Acids; D000970:Antineoplastic Agents
keywords: Amino acid derivatives; Antitumor properties; Apoptosis; Copper(I); Gold(I); Silver(I)