Selective inhibition of gastrointestinal beta-glucuronidase by poly(vinylbenzyl D-glucaro(1,4)lactonate). Part 2. Poly(vinylbenzyl D-glucaro(1,4) lactonate) in vitro inhibition studies.
In vitro inhibition studies with beta-glucuronidase from purified E. coli and mouse intestinal contents indicated that the polymer, poly(vinylbenzyl D-glucaro(1,4)lactonate, is an effective beta-glucuronidase inhibitor. Purified E. coli beta-glucuronidase was inhibited by 99.6% with 177 mM D-glucaro(1,4)lactone using the polymer-inhibitor. Similarly, 95% inhibition of beta-glucuronidase activity of mouse intestinal contents was obtained with 177 mM and 50% inhibition was obtained with 31.5 mM D-glucaro(1,4)lactone based on the modified polymer. The structural requirements of an effective beta-glucuronidase inhibitor based on the structure of the polymer-inhibitor are also discussed.
Sacco
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Environmental Health Sciences Program, School of Public Health, University of Massachusetts, Amherst 01003.
Calabrese
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EJ
D000818:Animals; D004355:Drug Stability; D004926:Escherichia coli; D005937:Glucaric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005966:Glucuronidase / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D011145:Polyvinyls / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D011145:Polyvinyls; C080605:polyvinylbenzyl glucaro(1,4)lactonate; C009194:saccharolactone; D005966:Glucuronidase; D005937:Glucaric Acid