Chemistry, antiproliferative properties, tumor selectivity and molecular mechanisms of novel gold(III) compounds for cancer treatment: a systematic study

The antiproliferative properties of a group of 13
structurally diverse gold(III) compounds, including six
mononuclear gold(III) complexes, five dinuclear oxobridged
gold(III) complexes, and two organogold(III)
compounds, toward several human tumor cell lines were
evaluated in vitro using a systematic screening strategy.
Initially all compounds were tested against a panel of 12human tumor cell lines, and the best performers were tested
against a larger 36-cell-line panel. Very pronounced antiproliferative
properties were highlighted in most cases,
with cytotoxic potencies commonly falling in the low
micromolar—and even nanomolar—range. Overall, goodto-
excellent tumor selectivity was established for at least
seven compounds, making them particularly attractive for
further pharmacological evaluation. Compare analysis
suggested that the observed antiproliferative effects are
caused by a variety of molecular mechanisms, in most
cases ‘‘DNA-independent,’’ and completely different from
those of platinum drugs. Remarkably, some new biomolecular
systems such as histone deacetylase, protein kinase
C/staurosporine, mammalian target of rapamycin/rapamycin,
and cyclin-dependent kinases were proposed for the
first time as likely biochemical targets for the gold(III)
species investigated. The results conclusively qualify
gold(III) compounds as a promising class of cytotoxic
agents, of outstanding interest for cancer treatment, while
providing initial insight into their modes of action.