Structural characterization and cytostatic activity of chlorobischolylglycinatogold(III)

Based on the ability of bile acids for vectorializing the cytostatic activi ty of other agents, we have designed and synthesized a new bile acid cholyl glycinato Au(III) complex, named Bamet-Al. It has been characterized by mea ns of EA (elemental analysis), FT-IR, NMR. FAB-MS (fast atom bombardment-ma ss spectrometry) and Vis-UV techniques. This characterization allowed us to propose a structure of the type [AuCG(O) CG(N,O) Cl] for the neutral compl ex, which has the composition C52H84N2O12AuCl and is very soluble in water, methanol, ethanol and DMSO (dimethylsulfoxide). The study in aqueous solut ion suggested a redox process for its transformation, which is accompanied by the appearance of colloidal gold phase. The behavior in 4 mM NaCl water tin 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 displa ys fluorescence. which does not change when incubated with DNA obtained fro m E. coli. Bamet-Al was found to inhibit the growth of a variety of cell li nes. The cytostatic effect was mild against human hepatoma HepG2. mouse hep atoma 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 unde r physiological conditions may explains the low cytostatic activity. (C) 20 01 Elsevier Science B.V. All rights reserved.