Inhibitory Effect of β-Glucosyl-Phenolic Hydroxamic Acids Against Urease in the Presence of Microfloral β-Glucosidase

Abstract

Three glucosyl-phenolic hydroxamates, 4-O-(β-D-glucopyranosyl) benzohydroxamic acid, 4-O-(β-D-glucopyranosyl) hippuric hydroxamic acid, and 3-[4-O-(β-D-glucopyranosyl) phenyl] propionohydroxamic acid (Glc-PPHA), were hydrolyzed to their corresponding aglycones by β-glucosidase of intestinal flora of rat without any major adverse hydrolysis in vitro. Inhibitory potency of these glucosyl-hydroxamates on urease was recovered to the same extent as that of the corresponding aglycone hydroxamates by preincubation for 2h with rat intestinal flora. p-Hydroxyphenylpropionohydroxamic acid inhibited noncompetitively jack-bean urease activity and its glucose-ligated form, Glc-PPHA inhibited it competitively. A single oral dose of Glc-PPHA tended to inhibit urease activity in proximal colon contents of rat at 6h after administration (p=0.06). After 14C-urea was orally administered to rat, 14CO2 was collected for to measure the ureolysis in vivo. Expired 14CO2 was limited to 40% by a single oral dose of Glc-PPHA during 6h, and 75% of intestinal ureolysis was repressed during the first 1h in the breath test. © 1995, The Pharmaceutical Society of Japan. All rights reserved.