Antitumoral Gold and Silver Complexes with Ferrocenyl-Amide Phosphines

The
monosubstituted ferrocenyl-amide phosphine ligands PPh2CH2CH2NHCOFc and (PPh2CH2CH2)2NCOFc and the disubstituted ferrocenyl-amide
diphosphine (PPh2CH2CH2NHCO)2Fc have been synthesized and used to prepare the gold chloride
derivatives [AuCl­(PPh2CH2CH2NHCOFc)],
[Au2Cl2{(PPh2CH2CH2)2NCOFc}], and [Au2Cl2{(PPh2CH2CH2NHCO)2Fc}] or the silver
species [Ag­(OTf)­(PPh2CH2CH2NHCOFc)2] and [Ag­(OTf)­(PPh3)­(PPh2CH2CH2NHCOFc)]. In the gold complexes the chloro ligands
can be easily substituted by several biologically relevant thiolates
such as 2-mercaptonicotinic acid, 2-thiocytosine, 2-thiouracil, 2-mercaptopurine,
and 2,3,4,6-tetra-6-acetyl-1-thiol-β-d-glucopyranosato,
affording the gold phosphine thiolate derivatives. In addition, the
gold phosphine thiolates of the closely related 1,1′-bis­(diphenylphosphine)­ferrocene
ligand have been prepared in order to compare their biological activities.
The antiproliferative activity of these compounds has been tested
by the MTT viability assay in two murine cell lines, NIH-3T3 (mouse
embryonic fibroblasts) and PC-12 (pheochromocytoma of the rat adrenal
medulla), and two human cell lines, A-549 (adenocarcinomic human alveolar
basal epithelial cells) and Hep-G2 (hepatocellular carcinoma). The
amide-phosphine ligands are not active, whereas the chloro-gold derivatives
have good antiproliferative activity in the murine cell lines and very
low activity in the human cell lines. The silver complexes are less
active than the gold derivatives. The gold thiolate complexes have
moderate to very good cytotoxic activity for all of the ligands, showing
excellent IC50 values for the thiolate complexes of the
amide-phosphines PPh2CH2CH2NHCOFc
and (PPh2CH2CH2N)2COFc
and dppf.