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Table of Contents
Vol. 58, No. 4, 2012
Issue release date: November 2012
Chemotherapy 2012;58:299–307
(DOI:10.1159/000343101)

New Anthraquinone Derivatives as Inhibitors of the HIV-1 Reverse Transcriptase-Associated Ribonuclease H Function

Esposito F. · Corona A. · Zinzula L. · Kharlamova T. · Tramontano E.
Department of Life and Environmental Sciences, University of Cagliari, Monserrato, Italy

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Abstract

Background: The degradative activity of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), termed ribonuclease H (RNase H), which hydrolyzes the RNA component of the heteroduplex RNA:DNA replication intermediate, is an excellent target for drug discovery. Anthraquinones (AQs) and their derivatives, which are common secondary metabolites occurring in bacteria, fungi, lichens and a large number of families in higher plants, have been reported to have several biological activities including that of inhibiting HIV-1 RT activities in biochemical assays. Methods: We have assayed new AQ derivatives on HIV-1 RNase H activities in biochemical assays. Results: Six series of new AQ derivatives with various substituents at positions 1, 2, 3 and 4 of the AQ ring were tested, and new analogs able to inhibit HIV-1 RT-associated RNase H activity in the low micromolar range were found. Conclusions: Our results demonstrate that AQ derivatives are promising anti-RNase H inhibitors.



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    External Resources

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