A group of triethylphosphine
gold(I) and
silver(I) complexes, structurally related to
auranofin, were prepared and investigated as potential anticancer drug candidates. The antiproliferative properties of these
metal compounds were assessed against two
leukemia cell lines, i.e., CCRF-CEM and its multidrug-resistant counterpart, CEM/ADR5000. Interestingly, potent cytotoxic effects were disclosed for both series of compounds against
leukemia cells, with IC50 values generally falling in the low-micromolar range, the
gold derivatives being on the whole more effective than the
silver analogues. Some initial structure-function relationships were drawn. Subsequently, the ability of the study compounds to inhibit the three main catalytic activities of the
proteasome was investigated. Different patterns of
enzyme inhibition emerged for the various
metal complexes. Notably,
gold compounds were able to inhibit effectively both the
trypsin-like and
chymotrypsin-like
proteasome activities, being less effective toward the
caspase-like catalytic activity. In most cases, a significant selectivity of the study compounds toward the
proteasome proteolytic activities was detected when compared to other
proteases. The implications of the obtained results are discussed.