Chemical behavior and in vitro activity of mixed phosphine gold(I) compounds on melanoma cell lines.
(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.
Caruso
Francesco
F
Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche (CNR), c/o University of Rome Istituto Chimico, Piazzale Aldo Moro 5, Rome, Italy. caruso@vassar.edu
Pettinari
Claudio
C
Paduano
Francesco
F
Villa
Raffaella
R
Marchetti
Fabio
F
Monti
Elena
E
Rossi
Miriam
M
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008545:Melanoma / Q000188:drug therapy*; D008958:Models, Molecular; D015394:Molecular Structure; D050607:Organogold Compounds / Q000737:chemistry* / Q000494:pharmacology*; D010720:Phosphines / Q000737:chemistry*; D013329:Structure-Activity Relationship
D050607:Organogold Compounds; D010720:Phosphines