Acyl Hydrazide Derivatives : A New Class of b-Glucuronidase Inhibitors

zyme that catalyzes the cleavage of glucuronosyl-O-bonds. The enzyme is present in many organs, body fluids, blood cells, liver, spleen, kidney, gastric juice, lung, muscle, bile, urine, and serum. It has been reported that in certain diseases such as cancer, inflammatory joint disease, some hepatic diseases, and AIDS the activity of b-glucuronidase increases. Human b-glucuronidase also has a role in the deconjugation of glycosaminoglycans. Endogenous biliary bglucuronidase deconjugates the glucuronides of bilirubin and causes the development of cholelithiasis in human bile. Many b-glucuronidase inhibitors such as 8-hydroxytricetin7-glucuronide and isovitexin, trihydroxy pipecolic acid, and scoparic acid A and C have already been isolated from different plants and some are used clinically. During random screening of synthetic compounds, we found that hydrazide derivatives can inhibit b-glucuronidase enzyme. Although these hydrazides are not stronger than other inhibitors but have comparable inhibitory activity, to the best of our knowledge, this is the first example of synthetic inhibitors of this enzyme. The present report describes the synthesis of a series of hydrazide derivatives and their bglucuronidase inhibitory activity with respect to structure– activity relationships.