7-phloroeckol and dieckol

SARS-CoV 3CL(pro) plays an important role in viral replication. In this study, we performed a biological evaluation on nine phlorotannins isolated from the edible brown algae Ecklonia cava. The nine isolated phlorotannins (1-9), except phloroglucinol (1), possessed SARS-CoV 3CL(pro) inhibitory activities in a dose-dependently and competitive manner. Of these phlorotannins (1-9), two eckol groups with a diphenyl ether linked dieckol (8) showed the most potent SARS-CoV 3CL(pro) trans/cis-cleavage inhibitory effects (IC(50)s = 2.7 and 68.1 μM, respectively). This is the first report of a (8) phlorotannin chemotype significantly blocking the cleavage of SARS-CoV 3CL(pro) in a cell-based assay with no toxicity. Furthermore, dieckol (8) exhibited a high association rate in the SPR sensorgram and formed extremely strong hydrogen bonds to the catalytic dyad (Cys145 and His41) of the SARS-CoV 3CL(pro).

Topics: Antiviral Agents; Benzofurans; Cysteine Proteases; Cysteine Proteinase Inhibitors; Humans; Molecular Docking Simulation; Phaeophyceae; Quantitative Structure-Activity Relationship; Severe Acute Respiratory Syndrome; Severe acute respiratory syndrome-related coronavirus

Pancreatic lipase is a potential therapeutic target for the treatment of diet-induced obesity in humans. In an ongoing search for new pancreatic lipase inhibitors from natural sources, a methanolic extract of marine brown algae, Eisenia bicyclis, showed a significant inhibitory effect against pancreatic lipase. Bioassay-guided isolation of this methanolic extract using a pancreatic lipase inhibitory assay led to the isolation and identification of six known phlorotannins: eckol (1), fucofuroeckol A (2), 7-phloroeckol (3), dioxindehydroeckol (4), phlorofucofuroeckol A (5), and dieckol (6). The structures were established on the basis of nuclear magnetic resonance and mass spectrometry spectroscopic data interpretation. Among the isolated phloroglucinol polymers, compounds 2 and 3 showed potent inhibitory effects on pancreatic lipase with IC₅₀ values ranging from 37.2 ± 2.3 to 12.7 ± 1.0 μM, respectively.

Topics: Animals; Benzofurans; Dioxins; Inhibitory Concentration 50; Lipase; Oxindoles; Phaeophyceae; Swine; Tannins

The present work investigates protein tyrosine phosphatase 1B (PTP1B) and the α-glucosidase inhibitory activities of two edible brown algae, Ecklonia stolonifera and Eisenia bicyclis, as well as in their isolated phlorotannins. Since the individual extracts and fractions showed significant inhibitory activities, column chromatography was performed to isolate six phlorotannins, phloroglucinol (1), dioxinodehydroeckol (2), eckol (3), phlorofurofucoeckol-A (4), dieckol (5), and 7-phloroeckol (6). Phlorotannins 3-6 were potent and noncompetitive PTP1B inhibitors with IC(50) values ranging from 0.56 to 2.64 µM; 4-6 exhibited the most potent α-glucosidase inhibition with IC(50) values ranging from 1.37 to 6.13 µM. Interestingly, 4 and 6 were noncompetitive, while 5 exhibited competitive inhibition in an α-glucosidase assay. E. stolonifera and E. bicyclis as well as their isolated phlorotannins therefore possessed marked PTP1B and α-glucosidase inhibitory activities; this could lead to opportunities in the development of therapeutic agents to control the postprandial blood glucose level and thereby prevent diabetic complications.

Topics: alpha-Glucosidases; Benzofurans; Blood Glucose; Complex Mixtures; Diabetes Mellitus; Dioxins; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Humans; Hyperglycemia; Hypoglycemic Agents; Kinetics; Magnetic Resonance Spectroscopy; Phaeophyceae; Phloroglucinol; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Solutions; Spectrophotometry; Tannins; Yeasts