Anti-Zika Virus Activity and Isolation of Flavonoids from Ethanol Extracts of Curatella americana L. Leaves.

The ethnomedicinal plant Curatella americana L. (Dilleniaceae) is a common shrub in the Brazilian Cerrado, whose ethanolic extract showed significant in vitro anti-Zika virus activity by the MTT colorimetric method. Currently, there is no drug in clinical use specifically for the treatment of this virus; therefore, in this work, the antiviral and cytotoxic properties of the ethanolic extract, fractions, and compounds were evaluated. The ethanolic extract of the leaves showed no cytotoxicity for the human MRC-5 cell and was moderately cytotoxic for the Vero cell (CC 50 161.5 ± 2.01 µg/mL). This extract inhibited the Zika virus multiplication cycle with an EC 50 of 85.2 ± 1.65 µg/mL. This extract was fractionated using the liquid-liquid partition technique, and the ethyl acetate fraction showed significant activity against the Zika virus with an EC 50 of 40.7 ± 2.33 µg/mL. From the ethyl acetate fraction, the flavonoids quercetin-3- O -hexosylgallate ( 1 ), quercetin-3- O -glucoside ( 2 ), and quercetin ( 5 ) were isolated, and in addition to these compounds, a mixture of quercetin-3- O -rhamnoside ( 3 ) and quercetin-3- O -arabinoside ( 4 ) was also obtained. The isolated compounds quercetin and quercetin-3-O-hexosylgallate inhibited the viral cytopathic effect at an EC 50 of 18.6 ± 2.8 and 152.8 ± 2.0, respectively. Additionally, analyses by liquid chromatography coupled to a mass spectrometer allowed the identification of another 24 minor phenolic constituents present in the ethanolic extract and in the ethyl acetate fraction of this species.