Isolation and structure elucidation of antioxidant compounds from stem and root barks of Daphne giraldii.

Two new compounds, aphegiractin A1/A2 (1a/1b), and seven known compounds were isolated by phytochemical work on EtOAc-soluble ingredients extracted from stem and root barks of Daphne giraldii. Their structures were established based on extensive spectroscopic methods, including HRESIMS, CD experiments, 1D and 2D NMR. All compounds were evaluated for their antioxidant activity to DPPH, ABTS radical scavenging activity and inhibitory activity on tyrosinase. Of these compounds, compound 3 exhibited significant antioxidant activities.

Prenylated flavonoids with significant anti-hepatoma activity from Daphne giraldii and effects on Fibroblast Growth Factor Receptor 1 (FGFR1).

We report here the orchestration of molecular ion networking (MoIN) and a set of computational and informatics assisted structural elucidation approaches in the discovery of 23 new prenyl-flavonoids and 13 known molecules from Daphne giraldii Nitsche (Thymelaeaceae), some of which possess significant bioactivity against hepatoma carcinoma. Daphnegiratriprenylone A (DPTP-A) represents the class of polyprenyl-flavonoids possessing a triprenyl substitution, and was identified with the guidance of mass spectrometry and nuclear magnetic resonance combined with computational approaches. This approach illustrates a paradigm shift in the application of computational tools for the direct assignment of new natural product structures and it was demonstrated to be reliable compared to conventional 2D-NMR techniques. Seventeen compounds exhibited potent and selective activity against Hep3B cells (IC50 ranging from 0.42 to 7.08 µM). Tyrosine kinase FGFR1 has emerged as a potential target of polyprenyl-flavonoids by a reverse pharmacophore mapping approach. We validated that the prenyl-flavonoids effectively inhibit FGFR1 using the Mobility Shift Assay, Western blot and molecular dynamics simulations, and the results suggest significant potency of the compounds towards FGFR1. These findings provide a new chemical class with strong links to traditional medicines, possessing reasonable safety for developing potential therapeutic agents for FGFR1-related diseases.