Complexes [Ag(H2BzPh)NO3] (1), [Ag(H2BzpCH3Ph)NO3] (2), [Ag(H2BzpClPh)NO3] (3), and [Ag(H2BzpNO2Ph)NO3] (4) were
synthesized with 2-benzoylpyridine benzoylhydrazone (H2BzPh) and its para-methyl-benzoylhydrazone (H2BzpCH3Ph), para-chloro-benzoylhydrazone (H2BzpClPh), and para-nitro-benzoylhydrazone
(H2BzpNO2Ph) derivatives. Experimental
data indicate that the nitrate ligand binds more strongly to the silver
center through one of the oxygen atoms, whereas the second oxygen
atom from nitrate and the hydrazone oxygen makes much weaker interactions
with the metal. Dissociation of nitrate most probably occurs in solution
and in biological media. Interestingly, theoretical calculations suggested
that when dissociation of the nitrate takes place, all bond orders
involving the metal and the atoms from the hydrazone ligand increase
significantly, showing that the bonding of nitrate results in the
weakening of all other interactions in the metal coordination sphere.
Upon complexation of the hydrazones to silver(I), cytotoxicity against
B16F10 metastatic murine melanoma cells increased in all cases. Complexes
(1–3) proved to be more cytotoxic than cisplatin.
All compounds were more cytotoxic to B16F10 cells than to nontumorigenic
murine Melan-A melanocyte cells. Interestingly, the selectivity index
(SI = IC50 non-malignant cells/IC50 tumor cells) of complex (1), SI =
23, was much higher than that of the parent hydrazone ligand, SI =
9.5. Studies on the interactions of complexes (1–3) with DNA suggested that although (1–3) interact
with calf thymus DNA by an intercalative mode, direct covalent binding
of silver(I) to DNA probably does not occur. Complexes (1–3) interact in vitro with human serum albumin indicating that these
compounds could be transported by albumin.