sciadopitysin and amentoflavone

As part of our search for botanical sources of SARS-CoV 3CL(pro) inhibitors, we selected Torreya nucifera, which is traditionally used as a medicinal plant in Asia. The ethanol extract of T. nucifera leaves exhibited good SARS-CoV 3CL(pro) inhibitory activity (62% at 100μg/mL). Following bioactivity-guided fractionation, eight diterpenoids (1-8) and four biflavonoids (9-12) were isolated and evaluated for SARS-CoV 3CL(pro) inhibition using fluorescence resonance energy transfer analysis. Of these compounds, the biflavone amentoflavone (9) (IC(50)=8.3μM) showed most potent 3CL(pro) inhibitory effect. Three additional authentic flavones (apigenin, luteolin and quercetin) were tested to establish the basic structure-activity relationship of biflavones. Apigenin, luteolin, and quercetin inhibited 3CL(pro) activity with IC(50) values of 280.8, 20.2, and 23.8μM, respectively. Values of binding energy obtained in a molecular docking study supported the results of enzymatic assays. More potent activity appeared to be associated with the presence of an apigenin moiety at position C-3' of flavones, as biflavone had an effect on 3CL(pro) inhibitory activity.

Topics: Apigenin; Biflavonoids; Binding Sites; Catalytic Domain; Computer Simulation; Coronavirus 3C Proteases; Cysteine Endopeptidases; Fluorescence Resonance Energy Transfer; Luteolin; Plant Leaves; Protease Inhibitors; Quercetin; Severe acute respiratory syndrome-related coronavirus; Structure-Activity Relationship; Taxaceae; Viral Proteins

Ginkgo biloba L. biflavones were shown to increase cAMP phosphodiesterase activity and to stimulate skin microcirculation. The aim of this study was to investigate whether biflavones were able to stimulate lipolysis in adipocytes. Lipolysis was assayed in fully differentiated 3T3-L1 fat cells in the presence of biflavones at 0.005 - 100 microM. Cell viability was evaluated at 0.5 -100 microM. Theophylline and caffeine were used as reference compounds. Lipolytic activity in untreated cells was 0.62 +/- 0.15 micromoles glycerol/mg DNA/h. All biflavones except sciadopitysin stimulated lipolysis in a concentration-dependent fashion. Maximal stimulation was observed at 0.1 - 0.5 microM. At higher concentrations the effect diminished progressively and was lost at 100 microM. Only a partial loss of cell viability was observed with biflavones at 10 - 100 microM.

Topics: 3T3 Cells; Adipocytes; Animals; Biflavonoids; Caffeine; Cell Survival; Dose-Response Relationship, Drug; Flavonoids; Ginkgo biloba; Lipolysis; Medicine, Chinese Traditional; Mice; Molecular Structure; Plant Extracts; Theophylline