Calystegine B4, a novel trehalase inhibitor from Scopolia japonica

• Published in: Carbohydrate research 1996-10, Vol.293 (2), p.195-204
• Main Authors: Asano, N, Kato, A, Kizu, H, Matsui, K, Watson, A.A, Nash, R.J
• Format: Article
• Language: English
• Subjects: Alkaloids - chemistry; Alkaloids - isolation & purification; Alkaloids - pharmacology; Animals; Binding, Competitive - physiology; Carbohydrate Conformation; chemical constituents of plants; chemical structure; enzyme inhibitors; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Gas Chromatography-Mass Spectrometry; Glycoside Hydrolases - antagonists & inhibitors; Intestines - enzymology; Kidney - enzymology; Kinetics; Magnetic Resonance Spectroscopy; Molecular Structure; Nortropanes - chemistry; Nortropanes - pharmacology; plant extracts; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plants - chemistry; purification; Rats; roots; Scopolia; Solanaceous Alkaloids; structure-activity relationships; Swine; trehalase; Trehalase - antagonists & inhibitors; tropane alkaloids; Tropanes
• ISSN: 0008-6215; 1873-426X
• DOI: 10.1016/0008-6215(96)00204-2

GLC-MS analysis has been developed for screening plants of the family Solanaceae for new calystegines. GLC-MS analyses of the extract of Scopolia japonica showed the presence of a new tetrahydroxy-nor-tropane alkaloid in addition to the known calystegines A3, A5, B1, B2, B3, and C1. We gave this new alkaloid the trivial name calystegine B4. The structure of calystegine B4 was determined as 1 alpha,2 beta,3 alpha,4 alpha-tetrahydroxy-nor-tropane from a variety of NMR spectral data. Calystegines B1, B2, and C1 are potent competitive inhibitors with Ki values ranging from 10(-6) to 10(-7) M for almond beta-glucosidase, while calystegine B4 inhibited this enzyme in a competitive manner, with a Ki value of 7.3 micromolar. Calystegine B2 is also a potent inhibitor of green coffee bean alpha-galactosidase, whereas calystegine B4 exhibited no significant activity for this enzyme. Among rat intestinal glycosidases, only trehalase was potently inhibited by calystegine B4, with an IC50 value of 9.8 micromolar. Furthermore, calystegine B4 potently inhibited pig kidney trehalase in a competitive manner, with a Ki value of 1.2 micromolar, but it was almost inactive against yeast and fungal trehalases.