Gold(III) complexes with bipyridyl ligands: solution chemistry, cytotoxicity and DNA binding properties

Gold(III) compounds generally exhibit significant cytotoxic effects on cancer cell lines and are
of potential interest as antitumor drugs. We report here on the solution chemistry, the
cytotoxicity, and the DNA binding properties of two new bipyridyl gold(III) compounds: [Au-
(bipy)(OH)2][PF6] (1) and the organometallic compound [Au(bipyc-H)(OH)][PF6] (2) (bipyc )
6-(1,1-dimethylbenzyl)-2,2¢-bipyridine). Both compounds are sufficiently soluble, and stable for
hours, within a physiological buffer at 37 °C; [Au(bipy)(OH)2][PF6], at variance with [Au(bipyc-
H)(OH)][PF6], is quickly and quantitatively reduced by ascorbate. Both compounds showed
relevant cytotoxic effects toward the A2780S, A2780R, and SKOV3 tumor cell lines; lower effects
were detected on the CCRF-CEM/S and CCRF-CEM/R lines. In most cases the mechanisms of
resistance to CDDP are only marginally effective against these gold(III) complexes. The
interactions of [Au(bipy)(OH)2][PF6] and [Au(bipyc-H)(OH)][PF6] with calf thymus DNA were
investigated in vitro by various techniques to establish whether DNA represents a primary
target for these compounds. Addition of saturating amounts of DNA did not affect appreciably
the visible spectra of these gold(III) complexes. Some slight modifications of the CD spectra of
calf thymus DNA and of the DNA melting parameters were observed; in any case, ultrafiltration
experiments showed that binding of these gold(III) complexes to DNA is weak and reversible.
The mechanistic implications of these findings are discussed.