Mphahlele, Morore and Papathanasopoulos, Maria and Cinellu, Maria Agostina and Coyanis, Mabel and Mosebi, Salerwe and Traut, Telisha and Modise, Refilwe and Coates, Judy and Hewer, Raymond (2012) Modification of HIV-1 reverse transcriptase and integrase activity by gold(III) complexes in direct biochemical assay. Bioorganic & Medicinal Chemistry, Vol. 20 (1), p. 401-407. eISSN 1464-3391. Article.
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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 μM in the direct HIV-1 RT assay, respectively, while IC50’s ranging from 0.461 to 8.796 μM 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 μM. 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.
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