Structural characterization and cytostatic activity of chlorobischolylglycinatogold(III).
Based on the ability of bile acids for vectorializing the cytostatic activity of other agents, we have designed and synthesized a new bile acid cholylglycinato Au(III) complex, named Bamet-A1. It has been characterized by means of EA (elemental analysis), FT-IR, NMR, FAB-MS (fast atom bombardment-mass spectrometry) and Vis-UV techniques. This characterization allowed us to propose a structure of the type [Au CG(O) CG(N,O) Cl] for the neutral complex, which has the composition C522H84N2O12AuCl and is very soluble in water, methanol, ethanol and DMSO (dimethylsulfoxide). The study in aqueous solution suggested a redox process for its transformation, which is accompanied by the appearance of colloidal gold phase. The behavior in 4 mM NaCl water (in order to mimic the cytoplasmatic fluid) was similar to that observed in water, while in a 150 mM NaCl (similar to extracellular fluid and serum), the apparition of a dark blue precipitate was observed. This complex displays fluorescence, which does not change when incubated with DNA obtained from E. coli. Bamet-A1 was found to inhibit the growth of a variety of cell lines. The cytostatic effect was mild against human hepatoma HepG2, mouse hepatoma Hepa 1-6, rat hepatoma McA RH-7777 and human colon adenocarcinoma LS-174T, and stronger against mouse sarcoma S180-II and mouse leukemia L-1210 cells. The appearance of colloidal Au during the process of hydrolysis under physiological conditions may explains the low cytostatic activity.
Carrasco
J
J
Departamento de Química Inorgánica, Universidad de Salamanca, Spain.
Criado
J J
JJ
Macías
R I
RI
Manzano
J L
JL
Marín
J J
JJ
Medarde
M
M
Rodríguez
E
E
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001647:Bile Acids and Salts / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003102:Colloids; D004269:DNA, Bacterial / Q000378:metabolism; D004926:Escherichia coli; D005453:Fluorescence; D006046:Gold; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D050607:Organogold Compounds; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D012965:Sodium Chloride / Q000494:pharmacology; D013057:Spectrum Analysis; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001647:Bile Acids and Salts; D003102:Colloids; D004269:DNA, Bacterial; D050607:Organogold Compounds; D009942:Organometallic Compounds; C439354:chlorobischolylglycinatogold(III); D012965:Sodium Chloride; D006046:Gold