| Summary: | Derived from the genus maple (Acer), acertannins are a group of gallotannins which have a characteristic 1,5-anhydro-d-glucitol (1,5-AG) occupying the central core position in the tannic acid structure whose hydroxyl groups have one or more galloyl residues. We have synthesized all ten naturally-occurring acertannins and seven new acertannin derivatives from 1,5-AG. Side-by-side comparisons revealed that 2,4,6-tri-O-galloyl-1,5-AG 21 (maplexin E) and maplexin F 22 (2,3,6-tri-O-galloyl-1,5-AG) were good inhibitors of ceramidase (CDase). In contrast, the core anhydrosugar 1,5-AG 12 itself and 3′,4′,5′-trimethoxy benzoyl derivatives 23–25 did not show CDase inhibition. Metabolic labelling experiments using NBD-hexanoic acid revealed that 50 μM of 6-O-galloyl-1,5-AG 16 (Ginnalin B), 2,6-di-O-galloyl-1,5-AG 19 (Ginnalin A), and 4,6-di-O-galloyl-1,5-AG 4 increased intracellular NBD-labeled ceramide, by 2.3, 2.2, and 2.1-fold, respectively. It is noteworthy that these acertannins 16, 19, and 4 promoted ceramide synthase 3 (CERS3) gene expression. Acertannins, therefore, represent a new class of potential intracellular ceramide regulators exhibiting both CDase inhibition and ceramide synthase promotion.
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