patuletin and kaempferol

Flaveria bidentis (L.) Kuntze is an annual alien weed of Flaveria Juss. (Asteraceae) in China. Bioactive compounds, mainly flavonol glycosides and flavones from F. bidentis (L.) Kuntze, have been studied in order to utilize this invasive weed, Analytical high-performance counter-current chromatography (HPCCC) was successfully used to separate patuletin-3-O-glucoside, a mixture of hyperoside (quercetin-3-O-galactoside) and 6-methoxykaempferol-3-O-galactoside, astragalin, quercetin, kaempferol and isorhamnetin using two runs with different solvent system. Ethyl acetate-methanol-water (10:1:10, v/v) was selected by analytical HPCCC as the optimum phase system for the separation of patuletin-3-O-glucoside, a mixture of hyperoside and 6-methoxykaempferol-3-O-galactoside, and astragalin. A Dichloromethane-methanol-water (5:3:2, v/v) was used for the separation of quercetin, kaempferol and isorhamnetin. The separation was then scaled up: the crude extract (ca 1.5 g) was separated by preparative HPCCC, yielding 12 mg of patuletin-3-O-glucoside at a purity of 98.3%, yielding 9 mg of a mixture of hyperoside and 6-methoxykaempferol-3-O-galactoside constituting over 98% of the fraction, and 16 mg of astragalin (kaempferol-3-O-glucoside) at a purity of over 99%. The pump-out peaks are isorhanetin (98% purity), kaemferol (93% purity) and quercitin (99% purity). The chemical structure of patuletin-3-O-glucoside and astragalin were confirmed by MS and ¹H, ¹³C NMR.

Topics: Chromones; Countercurrent Distribution; Flaveria; Flavonols; Glucosides; Kaempferols; Mass Spectrometry; Molecular Structure; Plant Extracts; Quercetin

A number of natural and synthetic flavonoids have been assessed previously with regard to their effects on the activity of cyclin-dependent kinases (Cdk1 and -2) related to the inhibition of cell cycle progression. On the other hand, the Cdk5/p35 system is of major importance in neuronal migration phenomena and brain development, and its deregulation is implicated in neurodegenerative diseases, particularly Alzheimer's. Here we show that some natural flavonoids inhibit the activity of the Cdk5/p35 system in the micromolar range, while others are practically inactive. Ring B-unsubstituted and highly methoxylated flavones were inactive or gave irreproducible results, and 6-methoxyapigenin and 6-methoxyluteolin were the most potent Cdk5 complex inhibitors within this series, while the common flavonols kaempferol and quercetin showed intermediate behavior. The reported crystal structure of the Cdk5 complex with its activator p25 was used for docking studies, which also led to the identification of the two 6-methoxyflavones, kaempferol and quercetin, as well as the untested 6-methoxy derivatives of kaempferol and quercetin and the corresponding 6-hydroxy analogues as compounds exhibiting a good fit to the active site of the enzyme.

Topics: Algorithms; Centaurea; Cyclin-Dependent Kinase 5; Cyclin-Dependent Kinases; Flavonoids; Flavonols; Inhibitory Concentration 50; Kaempferols; Molecular Conformation; Molecular Structure; Quercetin; Structure-Activity Relationship