Inhibitory Effect of β-Glucosyl-phenolic Hydroxamic Acids against Urease in the Presence of Microfloral β-Glucosidase

• Published in: Biological & pharmaceutical bulletin 1995/02/15, Vol.18(2), pp.208-213
• Main Authors: PARK, JongBeak, IMAMURA, Lisa, KOBASHI, Kyoichi, ITOH, Hisatomi, MIYAZAKI, Toshitsugu, HORISAKI, Toshio
• Format: Article
• Language: English
• Subjects: Animals; beta-Glucosidase - metabolism; Biological and medical sciences; Digestive system; Helicobacter pylori - enzymology; hepatic coma; hydroxamic acid; Hydroxamic Acids - chemistry; Hydroxamic Acids - pharmacology; Intestines - microbiology; Male; Medical sciences; Pharmacology. Drug treatments; pro-drug; Proteus mirabilis - enzymology; rat intestine; Rats; Rats, Wistar; urease; Urease - antagonists & inhibitors; β-glucosidase
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.18.208

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). After14C-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.