tosylphenylalanyl-chloromethyl-ketone and kaempferol

Phytochemical investigation of the whole plant of Lepisorus contortus (Christ) Ching led to the isolation of five new phenylethanoid glycosides (1-5), each containing a caffeoyl group, a new flavonoid glycoside (10), and 14 known compounds (6-9 and 11-15, syringic acid, vanillic acid, phloretic acid, diplopterol, and β-sitosterol). This is the first report of phenylethanoid glycosides from the family Polypodiaceae. Compounds 1-15 were evaluated for their cancer chemopreventive potential based on their ability to inhibit tumor necrosis factor alpha (TNF-α)-induced NF-κB activity, nitric oxide (NO) production, and aromatase, quinone reductase 2 (QR-2), and COX-1/-2 activities. Quercetin-3-O-β-d-glucoside (15) demonstrated inhibition against QR2 with an IC(50) value of 3.84 μM, which confirmed kaempferol/quercetin glycosides as the active compounds to inhibit QR2. The compound also demonstrated NF-κB activity with an IC(50) value of 33.6 μM. In addition, compounds 1, 2, 4, and 6 showed aromatase activity with IC(50) values of 30.7, 32.3, 26.8, and 35.3 μM, respectively.

Topics: Animals; Anticarcinogenic Agents; Antineoplastic Agents; Aromatase Inhibitors; Caffeic Acids; Cyclooxygenase Inhibitors; Drug Screening Assays, Antitumor; Flavonoids; Glycosides; Humans; Inhibitory Concentration 50; Kaempferols; Mice; Molecular Structure; NF-kappa B; Nitric Oxide; Polypodiaceae; Quercetin; Tumor Necrosis Factor-alpha

The effect of kaempferol on KCI (60 mM)-induced tonic contraction in isolated rat uterus and its modification by inhibitors of cAMP-dependent protein kinase (PKA) (Rp-cAMPS and TPCK), phosphodiesterase (papaverine), adenylyl cyclase (2',3'-dideoxyadenosine, DDA), transcription (actinomycin D), protein synthesis (cycloheximide) and ornithine decarboxylase (alpha-difluoromethyl-ornithine, DFMO), as well as a polyamine, spermine, have been assayed. Kaempferol (3 to 60 microM) induced concentration-dependent relaxation on KCl-induced tonic contraction (IC50: 10.1 +/- 1.89 microM). This relaxing effect was antagonized (p<0.05) by Rp-cAMPS (10 microM), TPCK (3 microM), DDA (100 microM), actinomycin D (4 and 12 microM), cycloheximide (100 microM), DFMO (10 mM), actinomycin D (12 microM) plus TPCK and actinomycin D (12 microM) plus spermine (1 mM). Furthermore, the displacement obtained with actinomycin D plus DFMO was not statistically significant. Our results suggest that kaempferol through cAMP produces transcriptional events and polyamines are, at least partially, involved in the relaxant effect of kaempferol.

Topics: Adenylyl Cyclase Inhibitors; Animals; Antimetabolites; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Cycloheximide; Dactinomycin; Dideoxyadenosine; Drug Synergism; Eflornithine; Enzyme Inhibitors; Female; Flavonoids; In Vitro Techniques; Kaempferols; Muscle Relaxation; Muscle, Smooth; Papaverine; Phosphodiesterase Inhibitors; Potassium Chloride; Protein Synthesis Inhibitors; Quercetin; Rats; Rats, Wistar; Serine Proteinase Inhibitors; Spermine; Thionucleotides; Tosylphenylalanyl Chloromethyl Ketone; Uterine Contraction; Uterus