Pyrazolate gold(I) derivatives. Preliminary biological evaluation of their anticancer properties

Pyrazolate gold(I) derivatives. Preliminary biological evaluation of their anticancer properties R. Galassi1, A. Burini1, S. Ricci1, C. Santini1, A. Dolmella2, M. P. Rigobello3, V. Gandin2 and C. Marzano2 University of Camerino, School of Science and Technology , I 1. -62032 – Camerino 2. University of Padova, Dept. Pharmaceutical Sciences, I-35131 – Padova 3. University of Padova, Dept. Biological Chemistry, I-35131 – Padova Pyrazolate gold(I) complexes is a well known class of gold(I) complexes readily obtained by reacting pyrazolates and Lgold(I)chloride precursors. Whether L in the gold precursor complex is dimethylsulphide, tetrahydrothiophene, triphenylarsine ligands dinuclear[1], trinuclear or polynuclear derivatives[2] can be obtained. On the other hand when the gold(I)chloride precursor contains a softer ligand such as phosphane the displacement is more difficult and mononuclear derivatives can be directly obtained. Mononuclear gold(I) derivative of diaryl or dialkyllpyrazolate and N-alkylimidazolate are reported in literature and they show peculiar features in the field of emission properties and material science.[3] However, their low solubility in polar solvents make difficult to considerate these compounds for biological targets. Figure 1. ORTEP structure for compound [3,5-dinitropyrazolategold(I)tris(phenyl)phosphane] Accordingly to the introduction of more polar substituents in the azoles a better water solubility can be achieved making possible their antitumoral evaluation. A series of mononuclear gold(I) pyrazolate and imidazolate complexes have been evaluated for their in vitro antitumor activity against a panel of human cancer cells some of which suitably selected for their resistance to cisplatin or belonging to Multi-Drug Resistance (MDR) phenotype. Since gold complexes have been validated as efficient inhibitors of the selenoprotein thioredoxin reductase (TrxR)[4], the most promising derivatives were also tested for the ability to inhibit cytosolic and mitochondrial TrxR. The inactivation of the closely related oxidoreductases glutathione reductase (GR) and glutathione peroxidase (GPx) was also examined. References 1. G. Yang, J. R. Martinèz, R. G. Raptis, Inorg. Chim. Acta. (2009), 362,1546. 2. H. H. Murray, R. G. Raptis, J. P. Fackler, Jr. Inorg. Chem. (1988), 27, 26 3. A. A. Mohamed, T. Grant, R. J. Staples, J. P. Fackler, Jr. Inorg. Chim. Acta, (2004), 354, 1761. 4. C.Marzano, V.Gandin, A.Folda, G.Scutari, A.Bindoli, M.P.Rigobello, Free Radic. Biol. Med. (2007), 42,