Inhibitory effect of beta-glucosyl-phenolic hydroxamic acids against urease in the presence of microfloral beta-glucosidase.
Three glucosyl-phenolic hydroxamates, 4-O-(beta-D-glucopyranosyl) benzohydroxamic acid, 4-O-(beta-D-glucopyranosyl)hippuric hydroxamic acid, and 3-[4-O-(beta-D-glucopyranosyl)phenyl]propionohydroxamic acid (Glc-PPHA), were hydrolyzed to their corresponding aglycones by beta-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 6 h 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 6 h, and 75% of intestinal ureolysis was repressed during the first 1 h in the breath test.
Park
J B
JB
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Imamura
L
L
Kobashi
K
K
Itoh
H
H
Miyazaki
T
T
Horisaki
T
T
D000818:Animals; D016480:Helicobacter pylori / Q000201:enzymology; D006877:Hydroxamic Acids / Q000737:chemistry / Q000494:pharmacology*; D007422:Intestines / Q000382:microbiology*; D008297:Male; D011513:Proteus mirabilis / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D014510:Urease / Q000037:antagonists & inhibitors*; D001617:beta-Glucosidase / Q000378:metabolism*
D006877:Hydroxamic Acids; D001617:beta-Glucosidase; D014510:Urease