2-Nitro and 4-nitro-quinone-methides are not irreversible inhibitors of bovine beta-glucuronidase.
4-Benzylamino-(and 4-chloromethyl)-2-nitro-beta-D-glucuronides (4, 10) and their 2-substituted-4-nitro regioisomers (7, 13) were prepared by glycosidation of the 3-nitro-4-hydroxy- and the 2-hydroxy-5-nitro-benzylic alcohol, respectively, with a glucuronyl donor. Carbonate activation followed by reaction with benzylamine or methanesulfonyl chloride afforded, after complete deprotection, the target molecules 4, 7, 10 and 13. These compounds have been synthesized to determine whether these molecules are (or not) glucuronidase inhibitors. After incubation with bovine liver beta-glucuronidase, none of the cleavage products (the titled quinone-methides) showed to be irreversible inhibitors of this enzyme.
Azoulay
M
M
Section de Recherche, UMR 176, CNRS-Institut Curie, 2 Paris, France.
Chalard
F
F
Gesson
J P
JP
Florent
J C
JC
Monneret
C
C
D000818:Animals; D002417:Cattle; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005966:Glucuronidase / Q000037:antagonists & inhibitors*; D045563:Indolequinones; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D015394:Molecular Structure; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry; D011809:Quinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D045563:Indolequinones; D007211:Indoles; D011355:Prodrugs; D011809:Quinones; C068040:quinone methide; D005966:Glucuronidase