Glycosidase inhibitors from the roots of Glyphaea brevis

作者：Gossan Diane Patricia Apie; Magid Abdulmagid Alabdul^*; Kouassi Yao Philomene Akoua; Behr Jean Bernard; Ahibo Antoine Coffy; Djakoure Leon Atoutou; Harakat Dominique; Voutquenne Nazabadioko Laurence

来源：Phytochemistry, 2015, 109: 76-83.

DOI：10.1016/j.phytochem.2014.10.029

• Iminosugars
• Nojirimycins
• Glycosidases inhibition
• Glyphaea brevis
• Malvaceae

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 A(1)-A(4) (1, 2, 5, 6), 1-deoxygalactonojirimycin in glyphaeaside B-1-B-5 (3, 4, 7-9) or 1-deoxynojirimycin in glyphaeaside C (10), substituted by a beta-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 beta-glucosidase with IC50 values ranging from 0.15 to 68 mu M. Compound 10 with an 1-deoxynojirimycin backbone was the most active and was found to act as a competitive inhibitor with K-i = 31 nM, therefore emerging as one of the most potent inhibitor of beta-glucosidase reported to date. Inhibition of beta-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 (alpha-glucosidase, alpha-fucosidase, alpha- and beta-galactosidase).

• 出版日期2015-1