Effect of 1-desoxynojirimycin derivatives on small intestinal disaccharidase activities and on active transport in vitro

Abstract

The influence of two new 1-desoxynojirimycin derivatives, BAY m 1099 and BAY o 1248, on rat small intestinal disaccharidases (sucrase, maltase, isomaltase. glucoamylase, lactase, trehalase) and alkaline phosphatase activity has been investigated in vitro. Both compounds are very potent α-glucosidase inhibitors. Tested in the range of 0.1-5.0 µg/ml, inhibition is strongest on sucrase (up to 97.1 %) and glucoamylase (up to 96.7%). BAY m 1099 also reduced (up to 56.4%) β-galactosidase (lactase) activity. For both inhibitors a competitive type of sucrase inhibition was demonstrated (Lineweaver-Burk plot). Affinity versus sucrase was unusually tight. The K i of BAY m 1099 versus sucrase amounted to 1.14 × 10 -7 M and of BAY o 1248 to 6.92 × 10 -8 M (Dixon plot). Both inhibitors did not impair active transport of L-leucine or methyl-α-D-glucoside into everted rings of rat jejunum in vitro. © 1985 S. Karger AG, Basel.