The influence of oxo-bridged binuclear gold(III) complexes on Na/K-ATPase activity: a joint experimental and theoretical approach.

The in vitro effects of oxo-bridged binuclear gold(III) complexes, i.e., [(bipy2Me)Au(μ-O)][PF] (Auoxo6), Au[(bipydmb-H)(μ-O)][PF] (AubipyC) and [Au(phen)(μ-O)](PF) (Auphen) on Na/K-ATPase, purified from the porcine cerebral cortex, were investigated. All three studied gold complexes inhibited the enzyme activity in a concentration-dependent manner achieving IC values in the low micromolar range. Kinetic analysis suggested an uncompetitive mode of inhibition for Auoxo6 and AubipyC, and a mixed type one for Auphen. Docking studies indicated that the inhibitory actions of all tested complexes are related to E2-P enzyme conformation binding to ion channel and intracellular part between N and P sub-domain. In addition, Auphen was able to inhibit the enzyme by interacting with its extracellular part as well. Toxic effects of the gold(III) complexes were evaluated in vitro by following lactate dehydrogenase activity in rat brain synaptosomes and incidence of micronuclei and cytokinesis-block proliferation index in cultivated human lymphocytes. All investigated complexes turned out to induce cytogenetic damage consisting of a significant decrease in cell proliferation and an increase in micronuclei in a dose-dependent manner. On the other hand, lactate dehydrogenase activity, an indicator of membrane integrity/viability, was not affected by Auoxo6 and AubipyC, while Auphen slightly modified its activity.