Glycosidase inhibitors from the roots of Glyphaea brevis

• Published in: Phytochemistry (Oxford) 2015-01, Vol.109, p.76-83
• Main Authors: Gossan, Diane Patricia Apie, Alabdul Magid, Abdulmagid, Kouassi-Yao, Philomène Akoua, Behr, Jean-Bernard, Ahibo, Antoine Coffy, Djakouré, Léon Atoutou, Harakat, Dominique, Voutquenne-Nazabadioko, Laurence
• Format: Article
• Language: English
• Subjects: Analytical chemistry; Chemical Sciences; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - isolation & purification; Glycosidases inhibition; Glycoside Hydrolases - antagonists & inhibitors; Glyphaea brevis; Imino Sugars - chemistry; Imino Sugars - isolation & purification; Iminosugars; Inhibitory Concentration 50; Life Sciences; Malvaceae; Malvaceae - chemistry; Molecular Structure; Nojirimycins; Pharmaceutical sciences; Plant Roots - chemistry
• ISSN: 0031-9422; 1873-3700
• DOI: 10.1016/j.phytochem.2014.10.029

Ten phenylalkyl-substituted iminosugars and a cinnamic acid derived glucoside were isolated from the roots of Gbrevis. Their structures were elucidated by spectroscopic studies and their inhibitory activity toward glycosidases was evaluated. [Display omitted] •Ten new phenylalkyl iminosugars were isolated from Glyphaea brevis.•Their structures were established on the basis of NMR spectroscopy and HRESIMS.•Their glycosidase inhibitory activity was evaluated.•A potent and selective inhibitor of β-glucosidase was identified. Ten phenylalkyl-substituted iminosugars (1–10) and a cinnamic acid derived glucoside (11) were isolated from the roots of Glyphaea brevis (Malvaceae). Their structures were elucidated by 1D and 2D NMR analysis, as well as by HR-ESIMS. Compounds 1–10 retain an unprecedented structure composed of an iminosugar-like core identified as 1-deoxyfuconojirimycin in glyphaeaside A1–A4 (1, 2, 5, 6), 1-deoxygalactonojirimycin in glyphaeaside B1–B5 (3, 4, 7–9) or 1-deoxynojirimycin in glyphaeaside C (10), substituted by a β-d-glucopyranose in compounds 2, 4, 6 and 9. These compounds feature a di-, tri- or tetra-hydroxylated nine-carbon chain at the pseudo-anomeric position, substituted by a terminal phenyl group. All alkyl C-iminosugars displayed potent and selective inhibition towards β-glucosidase with IC50 values ranging from 0.15 to 68μM. Compound 10 with an 1-deoxynojirimycin backbone was the most active and was found to act as a competitive inhibitor with Ki=31nM, therefore emerging as one of the most potent inhibitor of β-glucosidase reported to date. Inhibition of β-mannosidase was observed with compounds 1, 3, 7 and 10, but only weak inhibition could be detected with the alkyl-C-iminosugars on the other tested glycosidases (α-glucosidase, α-fucosidase, α- and β-galactosidase).