Modification of HIV-1 reverse transcriptase and integrase activity by gold(III) complexes in direct biochemical assays.

Gold(I) and gold(III) complexes have been previously investigated for potential biomedical applications
including as anti-HIV agents. The oxidising nature of some gold(III) complexes yields well-documented
cellular toxicity in cell-based assays but the effect in direct biochemical assays has not been fully investigated.
In this study, gold(III) complexes were evaluated in HIV-1 reverse transcriptase and HIV-1 integrase
biochemical assays. The gold(III) tetrachlorides KAuCl4 and HAuCl4 yielded sub-micromolar IC50’s of
0.947 and 0.983 lM in the direct HIV-1 RT assay, respectively, while IC50’s ranging from 0.461 to
8.796 lM were obtained for seven selected gold(III) complexes. The gold(III) tetrachlorides were also
effective inhibitors of integrase enzymatic activity with >80% inhibition obtained at a single dose
evaluation of 10 lM. RT inhibition was decreased in the presence of a reducing agent (10 mM DTT)
and against the M184V HIV-1 RT mutant, while none of the gold(III) complexes were effective inhibitors
in cell-based antiviral assays (SI values <5.95). Taken together, the findings of this study demonstrate that
gold(III) complexes modify HIV-1 enzyme activity in direct biochemical assays, most likely through protein
oxidation.