title: Glycosidase-inhibiting pyrrolidines and pyrrolizidines with a long side chain in Scilla peruviana.
abstract: 2,5-Dideoxy-2,5-imino-d-glycero-d-manno-heptitol (homoDMDP) is widely distributed in Hyacinthaceae plants and can also be regarded as the alpha-1-C-(1,2-dihydroxyethyl) derivative of 1,4-dideoxy-1,4-imino-d-arabinitol (d-AB1). In a search for glycosidase inhibitors in this family of plants, we isolated three new d-AB1 derivatives bearing the 2-hydroxypropyl (1), 1,2-dihydroxypropyl (2), and 1,5,7,12,13-pentahydroxytridecyl (3) side chains at the C-1alpha position, respectively, from the bulbs of Scilla peruviana. Alkaloid 3 was a powerful inhibitor of bacterial beta-glucosidase (IC(50) = 80 nM) and bovine liver beta-galactosidase (IC(50) = 90 nM). This plant coproduced four new pyrrolizidine alkaloids, alpha-5-C-(3-hydroxybutyl)-7-epi-australine (4), alpha-5-C-(3-hydroxybutyl)hyacinthacine A(1) (5), alpha-5-C-(1,3-dihydroxybutyl)hyacinthacine A(1) (6), and alpha-5-C-(1,3,4-trihydroxybutyl)hyacinthacine A(1) (7). Alkaloids 4 and 6 were potent inhibitors of yeast alpha-glucosidase, with IC(50) values of 6.6 and 6.3 microM, respectively, and alkaloid 6 was also a potent inhibitor of bacterial beta-glucosidase with an IC(50) value of 5.1 microM.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181, Japan. naoki22@po.incl.ne.jp
authors.forename: Naoki
authors.initials: N
authors.lastname: Asano
authors.forename: Kyoko
authors.initials: K
authors.lastname: Ikeda
authors.forename: Miyuki
authors.initials: M
authors.lastname: Kasahara
authors.forename: Yuko
authors.initials: Y
authors.lastname: Arai
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Kizu
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009426:Netherlands; D019906:Nuclear Magnetic Resonance, Biomolecular; D010407:Penicillium / Q000201:enzymology; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D011763:Pyrrolizidine Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D031445:Scilla / Q000737:chemistry*; D013237:Stereoisomerism; D015003:Yeasts / Q000201:enzymology
chemical_list: D004791:Enzyme Inhibitors; D011759:Pyrrolidines; D011763:Pyrrolizidine Alkaloids; D006026:Glycoside Hydrolases