Chemical behavior and in vitro activity of mixed phosphine gold(I) compounds on melanoma cell lines.

Abstract

(31)P nuclear magnetic resonance and electrospray ionization-mass spectrometry studies on the melanoma cytotoxic chlorotriphenylphosphine-1,3-bis(diphenylphosphino)propanegold(I), [Au(DPPP)(PPh 3)Cl], show partial decomposition that includes the novel dinuclear cation [Au 2(DPPP) 2Cl] (+); its structure was calculated by using the density functional theory (DFT). Unexpectedly, by using the diphosphine ligand 1,2-bis(diphenylphosphino)ethane (DIPHOS), [{AuCl(PPh 3)} 2(mu 2-DIPHOS)] was obtained. Its X-ray crystal structure shows a unique triangular coordination sphere in contrast to the T-shaped geometry of related Au(I)-DIPHOS compounds. Its cytotoxic activity in JR8, SK-Mel-5, and 2/60 melanoma cell lines is dose-dependent and lower than that of [Au(DPPP)(PPh 3)Cl] because of its nonchelating nature. An in vitro study of the effect of both Au compounds on the B16V melanoma cell line gives credence to this structure-activity relationship. IC 50 indicates that both Au species are 10 times more active in B16V than in JR8, SK-Mel-5, and 2/60. Oxidation of [Au(DPPP)(PPh 3)Cl] toward Au(III) compounds and phosphine-oxides is observed upon reaction with hypochlorite in water/dimethyl sulfoxide solution, mimicking endogenous hypochlorite. A related reaction involving the formation of [AuCl 4] (-) is thermodynamically feasible according to DFT calculations.

• Authors: Francesco Caruso, Claudio Pettinari, Francesco Paduano, Raffaella Villa, Fabio Marchetti, Elena Monti, Miriam Rossi
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 51 Issue 6 Pg. 1584-91 (Mar 27 2008) ISSN: 0022-2623 [Print] United States
• PMID: 18307291 (Publication Type: Journal Article)

Chemical References

• Organogold Compounds
• Phosphines

Topics

• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Crystallography, X-Ray
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Humans
• Melanoma (drug therapy)
• Models, Molecular
• Molecular Structure
• Organogold Compounds (chemistry, pharmacology)
• Phosphines (chemistry)
• Structure-Activity Relationship