Effects of New Quinizarin Derivatives on Both HCV NS5B RNA Polymerase and HIV-1 Reverse Transcriptase Associated Ribonuclease H Activities

Abstract

Human immunodeficiency virus 1 (HIV-1) and Hepatitis C virus (HCV) affect 60 and 170 million infected individuals worldwide, respectively, and co-infection by both pathogens is often observed. This represents a serious public health problem that requires the identification of new drugs targeting essential phases of the life cycle of these two viruses. In this report, the synthesis and inhibitory activity of quinizarin derivatives towards both HCV NS5B polymerase and HIV-1 reverse transcriptase associated functions are reported. Our results demonstrate that anthraquinone derivatives are promising anti-polymerase viral inhibitors.

Active Site and Allosteric Inhibitors of the Ribonuclease H Activity of HIV Reverse Transcriptase

“…Screening of plant natural metabolites amide identified a new series of emodin [49] and alizarin anthraquinone derivatives [50,51] that inhibited both HIV-1 RT and HCV RNA polymerase [15]. Interestingly, compound 1-acetoxy-9,10-dioxo-9,10-dihydroanthracen-2-yl-4-bromobenzoate (KNA-53, 27 ; FIGURE 7) inhibited both RNaseH and RNA-dependent DNA polymerase activity of wt and Lys103Asn RTs (IC 50 = 22 and 9 μM, respectively) but only the RNaseH function of Tyr181Cys RT (IC 50 = 22 μM).…”

Sennoside A, derived from the traditional chinese medicine plant Rheum L., is a new dual HIV-1 inhibitor effective on HIV-1 replication

“…A number of polyphenol derivatives, including, for instance, anthraquinones, have been reported to interfere with the life cycle of different viruses, among which encephalomyocarditis virus in mice (Barnard et al 1992), human cytomegalovirus (Barnard et al 1992;Bamard et al 1995), poliovirus (Semple et al 2011) and hepatitis B virus (Dang et al 2006), as well as to inhibit the catalytic activity of HCV NS5B Polymerase (Tramontano et al 2011) and HIV-1 RT (Tramontano et al 2011;Higuchi et al 1991;Esposito et al 2011;Kharlamova et al 2009) and integrase (IN) functions in biochemical assays (Tintori et al 2015;Esposito et al 2015). In particular, a number of anthraquinone derivatives were reported to affect both HIV-1 RDDP and RNase H RT-associated functions in biochemical assays, but were not active on viral replication in cell-based assays (Tramontano et al 2011;Higuchi et al 1991;Esposito et al 2011;Kharlamova et al 2009). Hence, we wanted to evaluate the effects of the chemical components originated from the Rheum Chinese plants to inhibit the HIV-1 RT-associated and IN activities and to interfere with the HIV-1 life cycle in order to identify new scaffold inhibiting multiple HIV-1 targets.…”

Hypericum hircinumL. components as new single-molecule inhibitors of both HIV-1 reverse transcriptase-associated DNA polymerase and ribonuclease H activities

“…The prophylactic and therapeutic action of natural extracts on viral diseases has been known since ancient times. In the last years, many reports have been published describing the antiviral activity exerted by plant components such as, for example, anthraquinones, which show antiviral effects on human cytomegalovirus (Barnard et al, 1992), hepatitis B virus (Shuangsuo et al, 2006), Epstein-Barr virus activation (Koyama et al, 2006), and HIV-1 RT activity (Kharlamova et al, 2009;Esposito et al, 2011Esposito et al, , 2012bTramontano et al, 2011). Recently, a few studies have been published on Hypericum hircinum L., an evergreen shrub belonging to the Hypericaceae family, widely used in Lucanian folk medicine for the treatment of cough (Pieroni et al, 2004) and in Sardinian medicine for its antiseptic properties and burns treatment (Ballero et al, 1997).…”