Bisbenzylisoquinoline alkaloids of Cissampelos sympodialis with antiviral activity against dengue virus

Abstract

A number of bisbenzyilisoquinoline alkaloids have been previously isolated from Cissampelos 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 IC₅₀ of 2.00 µg/mL and a selectivity index (SI) of 10.74. Warifteine was the second most active sample and had an IC₅₀ of 8.13 µg/mL and SI = 10.94. The antiviral activity of the samples compared favorably with that of 6-methylmercaptopurine riboside (IC₅₀ = 7.31 µg/mL and SI = 11.8). These results suggest that bisbenzylisoquinoline alkaloids may prove interesting leading antiviral compounds.

Keywords:

• Cissampelos sympodialis
• dengue virus
• antiviral activity
• warifteine
• methylwarifteine
• bisbenzylisoquinoline alkaloids

Acknowledgement

The authors are also grateful to Dr. Vicente Carlos de Oliveira Costa from Federal University of Paraiba, Brazil for NMR spectral data.

Disclosure statement

The authors have no conflicts of interest to disclose.

Additional information

Funding

The authors are grateful to FAPEMIG (research grant APQ-00523-15 for E. J. Oliveira and MSc grant of A. H. Fonseca). P. G. da Silva is a recipient of a MSc fellowship from the Pernambuco State Foundation for Science and Technology of Pernambuco (FACEPE). T. M. S. Da Silva is grateful to FACEPE (Grant no. PRONEM APQ-0741106/2014).