title: HCV-NS3/4A protease inhibitory iridoid glucosides and dimeric foliamenthoic acid derivatives from Anarrhinum orientale.
abstract: Four new compounds were isolated from the methanol extract of the aerial parts of Anarrhinum orientale: 6'-O-cinnamoylmussaenosidic acid (1), 6'-O-cinnamoyl-8-O-(6'''-O-cinnamoylglucopyranosyl)mussaenosidic acid (2), (2E,6E)-8-{[(2E,6E)-8-hydroxy-2,6-dimethylocta-2,6-dienoyl]oxy}-2,6-dimethylocta-2,6-dienoic acid (3), and (2E,6E)-8-{[(2E,6E)-8-acetoxy-2,6-dimethylocta-2,6-dienoyl]oxy}-2,6-dimethylocta-2,6-dienoic acid (4). The known 8-O-cinnamoylmussaenosidic acid (5) was also identified. All five compounds were tested for inhibition of the hepatitis C virus (HCV) protease. Compounds 1 and 5 exhibited moderate activity, while 2 and 3 showed weak effects. No inhibitory activity on the human serine protease was observed for any of these compounds, which may infer the selectivity toward the viral protease. A computational docking study of the isolated compounds against HCV protease was used to formulate a hypothetical mechanism for the inhibitory activity of the active compounds on the enzymes tested.
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
authors.forename: Riham
authors.initials: R
authors.lastname: Salah El Dine
authors.forename: Azza R
authors.initials: AR
authors.lastname: Abdel Monem
authors.forename: Ali M
authors.initials: AM
authors.lastname: El-Halawany
authors.forename: Masao
authors.initials: M
authors.lastname: Hattori
authors.forename: Essam
authors.initials: E
authors.lastname: Abdel-Sattar
mesh_terms: D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D057888:Iridoid Glucosides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000494:pharmacology; D012529:Saudi Arabia; D028083:Scrophulariaceae / Q000737:chemistry*; D057057:Serine Proteases / Q000187:drug effects; D013237:Stereoisomerism; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D005231:Fatty Acids, Unsaturated; D057888:Iridoid Glucosides; D011480:Protease Inhibitors; D057057:Serine Proteases; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases