title: In vitro and in vivo evaluation of organometallic gold(I) derivatives as anticancer agents.
abstract: Alkyne gold(I) derivatives with the water soluble phosphanes PTA (1,3,5-triaza-7-phosphaadamantane) and DAPTA (3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane) were described and their anticancer potential against the colon cancer cell line Caco-2 (PD7 and TC7 clones) was studied. Strong antiproliferative effects are found, for all the new complexes, to be even more pronounced than for the reference drug cisplatin, and similar to auranofin. The interaction of these derivatives with bovine serum albumin (BSA) was studied by fluorescence spectroscopy. The types of quenching and binding constants were determined by a fluorescence quenching method. Moderate values of the binding constants are calculated for the tested derivatives indicating that these complexes can be stored and carried easily by this protein in the body. The study of the thermodynamic parameters in the case of [Au(C[triple bond, length as m-dash]CCH2Spyridine)(PTA)] points out to the presence of van der Waals interactions or hydrogen bonding between the metallic complex and the protein. In addition, the complex [Au(C[triple bond, length as m-dash]CCH2Spyridine)(PTA)] has shown inhibition in colon cancer proliferation of HTC-116-luc2 cell lines via the apoptotic pathway and S-phase arrest of the cell cycle. Intraperitoneal injection of this derivative in athymic nude mice inoculated with HTC-116-luc2 cells prolonged their survival and displayed moderate inhibition of the tumour growth with no subsequent organ (kidney and liver) damage after treatment.
authors.affiliation: Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea-ISQCH, Universidad de Zaragoza-C.S.I.C., 50009 Zaragoza, Spain. mlaguna@unizar.es ecerrada@unizar.es.
authors.forename: Elena
authors.initials: E
authors.lastname: García-Moreno
authors.forename: Alejandro
authors.initials: A
authors.lastname: Tomás
authors.forename: Elena
authors.initials: E
authors.lastname: Atrián-Blasco
authors.forename: Sonia
authors.initials: S
authors.lastname: Gascón
authors.forename: Eduardo
authors.initials: E
authors.lastname: Romanos
authors.forename: Mary Jesus
authors.initials: MJ
authors.lastname: Rodriguez-Yoldi
authors.forename: Elena
authors.initials: E
authors.lastname: Cerrada
authors.forename: Mariano
authors.initials: M
authors.lastname: Laguna
mesh_terms: D000480:Alkynes / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001310:Auranofin / Q000494:pharmacology; D018938:Caco-2 Cells; D002417:Cattle; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000401:mortality; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006046:Gold / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010720:Phosphines / Q000737:chemistry; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D015996:Survival Rate; D014183:Transplantation, Heterologous
chemical_list: D000480:Alkynes; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D010720:Phosphines; D012710:Serum Albumin, Bovine; D001310:Auranofin; D006046:Gold; C044646:phosphine; D002945:Cisplatin