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.
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.
Authors: Maria Barbara Pisano; Sofia Cosentino; Silvia Viale; Delia Spanò; Angela Corona; Francesca Esposito; Enzo Tramontano; Paola Montoro; Carlo Ignazio Giovanni Tuberoso; Rosaria Medda; Francesca Pintus Journal: Biomed Res Int Date: 2016-05-24 Impact factor: 3.411