In vitro evaluation of anthraquinones from Aloe vera (Aloe barbadensis Miller) roots and several derivatives against strains of influenza virus

Aloe vera is a crop of wide economic value of worldwide distribution, and a rich source of quinone components. Recently, antiviral aloe anthraquinones had been reported against human influenza virus. In the present work two anthraquinones, aloesaponarin-I (1) and aloesaponarin-II (2) were isolated from A. vera roots, and six derivatives were obtained by methylation (3), acetylation (4) and O-glycosyl (5-6) reactions starting from (1). Additionally, a new Tetra-O-acetyl-β-d-glucopyranosyl derivative from 2 was also prepared. All compounds were evaluated against two strains of influenza virus AH1N1 by cytopathic effect reduction assay (CPE). The antiviral activity was determined by the ability of compounds to inhibit virus replication on Madin Darby Canine Kidney cells (MDCK). New derivatives 3-(2´,3´,4´,6´-Tetra-O-acetyl-β-d-glucopyranosyl-aloesaponarin-I (5) and 3-(2´,3´,4´,6´-Tetra-O-acetyl-β-d-glucopyranosyl- aloesaponarin-II (7) showed a cytopathic reduction effect against influenza strain A/Yucatán/2370/09 with IC(50) of 30.77 and 13.70 μM, and against the virus A/Mexico/InDRE797/10 with IC(50) of 62.28 and 19.47 μM, respectively. To assess the effect of derivatives 5 and 7 during one cycle of replication (0–10 h), a time-of-addition experiment was performed. As a result it was found that both compounds were most effective when added 6–10 h post-infection and significantly inhibited viral titre (> 70%) at the concentrations of 50 and 100 μM. Based on the structural analysis of the compounds, it was suggested that the Tetra-O-acetyl-β-d-glucopyranosyl substituent at the C3 position of the anthraquinone might have an effect against the influenza AH1N1 virus.