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

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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DOI: 10.1016/j.bmc.2011.10.072

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 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.

Item Type:Article
ID Code:8237
Status:Published
Refereed:Yes
Uncontrolled Keywords:Gold complexes, HIV-1 reverse transcriptase, oxidation
Subjects:Area 03 - Scienze chimiche > CHIM/03 Chimica generale e inorganica
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Chimica e Farmacia
Publisher:Pergamon / Elsevier
eISSN:1464-3391
Deposited On:07 Jan 2013 12:03

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