2-Nitro and 4-nitro-quinone-methides are not irreversible inhibitors of bovine beta-glucuronidase

Carbohydr Res. 2001 May 18;332(2):151-6. doi: 10.1016/s0008-6215(01)00083-0.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Glucuronidase / antagonists & inhibitors*
  • Indolequinones*
  • Indoles / chemical synthesis
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Liver / enzymology
  • Molecular Structure
  • Prodrugs / chemical synthesis
  • Prodrugs / chemistry
  • Quinones / chemical synthesis
  • Quinones / chemistry
  • Quinones / pharmacology*
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Indolequinones
  • Indoles
  • Prodrugs
  • Quinones
  • quinone methide
  • Glucuronidase