Abstract
Here we report the evaluation of the antiretroviral effect of two flavonoid 7-O-glucosides, herbacitrin (1) and gossypitrin (2), together with quercetin (3), a well-studied flavonol. Antiviral activity of the flavonoids was assessed by analyzing HIV-1 p24 core protein levels in the supernatants of HIV-1 infected MT-4 and MT-2 cell cultures. The compounds showed mild to weak cytotoxic activities on the host cells; herbacitrin was the strongest in this regard (CC50=27.8 and 63.64 μM on MT-4 and MT-2 cells, respectively). In nontoxic concentrations, herbacitrin and quercetin reduced HIV-1 replication, whereas gossypitrin was ineffective. Herbacitrin was found to inhibit reverse transcriptase at 21.5 μM, while it was a more potent integrase inhibitor already active at 2.15 μM. Therefore, our observations suggest that herbacitrin exerts antiretroviral activity through simultaneously acting on these two targets of HIV-1 and that integrase inhibition might play a major role in this activity.
Highlights
Human immunodeficiency virus type 1 (HIV-1) is the causative agent of acquired immune deficiency syndrome (AIDS)
Herbacitrin (1) and gossypitrin (2) have been first isolated from cotton flowers (Gossypium herbaceum), [18] and later both compounds were detected in different Equisetum species [19, 20]
Gossypitrin was identified in yellow petals of Papaver nudicaule, [21] and flowers of Talipariti elatum [22]
Summary
Human immunodeficiency virus type 1 (HIV-1) is the causative agent of acquired immune deficiency syndrome (AIDS). Previous studies showed that different types of flavonoids, especially certain flavonols, flavones, isoflavones, catechin derivatives, and chalcones, can act as multitarget agents through simultaneously inhibiting crucial enzymes of HIV1 (RT, IN, and PR) and interfering with different steps of the virus’ life cycle [11] In this regard, the most studied flavonoid is quercetin that was reported to exert significant anti-HIV activity by inhibiting HIV replication and to reduce virus infectivity in normal peripheral blood mononuclear cells (PBMC) [12]. The above findings suggest that quercetin analogs, and especially 7-O-glycosylated compounds with an additional hydroxyl group at their ring A, are worthy of studying as antiretroviral agents In pursuing this notion, we selected two such compounds, herbacitrin (1) and gossypitrin (2) (Figure 1), constituents of many Asian medicinal plants, for investigating their in vitro cytotoxicity, anti-HIV-1 activity, and reverse transcriptase and integrase inhibitory activity. The data were compared with those of quercetin, which served as a well-established positive control in our study presented hereinafter
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