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.

Modification of HIV-1 reverse transcriptase and integrase activity by gold(III) complexes in direct biochemical assays / Mphahlele, M; Papathanasopoulous, M; Cinellu, Maria Agostina; Mosebi, S; Traut, Tt; Coyanis, M; Modise, R; Coates, J; Hewer, R.. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - 20:(2012), pp. 401-407. [10.1016/j.bmc.2011.10.072]

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

CINELLU, Maria Agostina;
2012

Abstract

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.
Modification of HIV-1 reverse transcriptase and integrase activity by gold(III) complexes in direct biochemical assays / Mphahlele, M; Papathanasopoulous, M; Cinellu, Maria Agostina; Mosebi, S; Traut, Tt; Coyanis, M; Modise, R; Coates, J; Hewer, R.. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - 20:(2012), pp. 401-407. [10.1016/j.bmc.2011.10.072]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/84954
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