title: A potential antitumor agent, (6-amino-1-methyl-5-nitrosouracilato-N3)-triphenylphosphine-gold(I): structural studies and in vivo biological effects against experimental glioma.
abstract: The synthesis and molecular and supramolecular structures of the compound (6-amino-1-methyl-5-nitrosouracilato-N3)-triphenylphosphine-gold(I) with interesting abilities to inhibit tumor growth in an animal model of experimental glioma are reported. Thus, its antitumor properties, effects on both enzyme and non-enzyme antioxidant defense systems and the response of several biochemical biomarkers have been analyzed. After seven days of treatment, the gold compound decreased the tumor growth to ca. one-tenth and reduced oxidative stress biomarkers (thiobarbituric acid-reactive substances (TBARS) and protein oxidation levels) compared to animals treated with the vehicle. Also, gold compound maintained non-enzyme antioxidant defense systems as in non-tumor animals and increased enzyme antioxidant defenses, such as superoxide dismutase and glutathione peroxidase activities, and decreased catalase activity. Analysis of serum levels of electrolytes, nitrogenous compounds, glucose, lipids, total protein, albumin, transaminases and alkaline phosphatase indicated that gold compound treatment showed few adverse effects, while effectively inhibiting tumor growth through mechanisms that involved endogenous antioxidant defenses.
authors: Department of Inorganic and Organic Chemistry, University of Jaén, Spain.
authors: Nuria A
authors: NA
authors: Illán-Cabeza
authors: Antonio R
authors: AR
authors: García-García
authors: José M
authors: JM
authors: Martínez-Martos
authors: María J
authors: MJ
authors: Ramírez-Expósito
authors: Tomás
authors: T
authors: Peña-Ruiz
authors: Miguel N
authors: MN
authors: Moreno-Carretero
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D050607:Organogold Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014498:Uracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: C584133:(6-amino-1-methyl-5-nitrosouracilato-N3)triphenylphosphinegold(I); D000970:Antineoplastic Agents; D000975:Antioxidants; D050607:Organogold Compounds; D014498:Uracil