Flacourtosides A–F, Phenolic Glycosides Isolated from Flacourtia ramontchi

Abstract

In an effort to identify novel inhibitors of chikungunya (CHIKV) and dengue (DENV) 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 DENV 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 poliothrysoside, and betulinic acid 3β-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 DENV RNA polymerase assay, significant inhibition was observed with betulinic acid 3β-caffeate (IC(50) = 0.85 ± 0.1 μM) and to a lesser extent for the flacourtosides A and E (1 and 5, respectively), and scolochinenoside D (IC(50) values ~10 μM).

Chikungunya fever: Epidemiology, clinical syndrome, pathogenesis and therapy

“…Similarly, products extracted from the leaves of the Madagascan plant Anacolosa pervilleana, demonstrated moderate activity in vitro against CHIKV replication (Bourjot et al, 2012b;Bourjot et al, 2012c). More recently, Kaur et al (2013) identified amongst a highly purified natural product compound library, a cephalotaxine alkaloid called harringtonine that displayed potent inhibition of CHIKV infection affecting CHIKV RNA production as well as viral protein expression with minimal cytotoxicity.…”

Chemical constituents of Anacolosa pervilleana and their antiviral activities

“…Evaluation of the selective antiviral activity of (5) and (6) virus-cell-based assay for SFV and SINV did show some antiviral effect (data not shown), but no 100% inhibition of virus-induced CPE was observed as for CHIKV (for all three assays, the same Vero cell line was used). In a previous study we found that betulinic acid 3β-caffeate elicited a significant inhibitory effect on the replication of CHIKV but with some cytotoxic activity [23]. Recently, a series of oleanan-type triterpenoids including glycyrrhizin and its aglycone, glycyrrhetic acid, were shown to possess anti-herpes simplex virus type 1 (HSV-1) activity in vitro [24].…”

Potential Antivirals: Natural Products Targeting Replication Enzymes of Dengue and Chikungunya Viruses

“…This is an important approach since inhibition of these enzymes can disrupt virus life cycle. Most of the studies herein described were conducted in vitro using enzymatic assays [8,[47][48][49][50][51][52] or viral strain/replicon on cells evaluating replication, inhibition and/or protein expression [49, 51-54, 56, 68-71. Three studies were conducted utilizing in silico docking approach [57,58,72].…”