Flacourtosides A-F, Phenolic Glycosides Isolated from Flacourtia ramontchi

In an effort to identify novel inhibitors of chikungunya (CHIKV) and dengue (DENY) virus replication, a systematic study with 820 ethyl acetate extracts of madagascan plants was performed in a virus-cell-based assay for CHIKV, and a DENY NS5 RNA-dependent RNA polymerase (RdRp) assay. The extract obtained from the stem bark of Flacourtia ramontchi was selected for its significant activity in both assays. Six new phenolic glycosides, named flacourtosides A-F (1-6), phenolic glycosides itoside H, xylosmin, scolochinenoside D, and polio-thrysoside, and betulinic acid 3 beta-caffeate were obtained using the bioassay-guided isolation process. Their structures were elucidated by comprehensive analyses of NMR spectroscopic and mass spectrometric data. Even though several extracts and fractions showed significant selective antiviral activity in the CHIKV virus-cell-based assay, none of the purified compounds did. However, in the DENY RNA polymerase assay, significant inhibition was observed with betulinic acid 3 beta-caffeate (IC50 = 0.85 +/- 0.1 mu M) and to a lesser extent for the flacourtosides A and E (1 and 5, respectively), and scolochinenoside D (IC50 values similar to 10 mu M).