Bisbenzylisoquinoline alkaloids ofCissampelos sympodialiswith antiviral activity against dengue virus

A number of bisbenzyilisoquinoline alkaloids have been previously isolated fromCissampelos sympodialis(Menispermaceae). The tertiary alkaloid fraction of the rhizomes (TAFrz) was prepared and the major alkaloid warifteine was isolated. Five TAFrz subfractions in addition to warifteine were tested against Dengue virus (DENV). We then used an epithelial (Vero) cell line to evaluate the cytotoxicity and effective concentrations of the samples against DENV. All TAFrz subfractions were active, but subfraction 6 (a mixture of the alkaloids methylwarifteine and warifteine) in particular showed a promising antiviral effect against DENV-2 with an IC(50)of 2.00 mu g/mL and a selectivity index (SI) of 10.74. Warifteine was the second most active sample and had an IC(50)of 8.13 mu g/mL and SI = 10.94. The antiviral activity of the samples compared favorably with that of 6-methylmercaptopurine riboside (IC50= 7.31 mu g/mL and SI = 11.8). These results suggest that bisbenzylisoquinoline alkaloids may prove interesting leading antiviral compounds.