DBU-assisted cyclorelease elimination: combinatorial synthesis and gamma-glutamyl cysteine synthetase and glutathione-S-transeferase modulatory effect of C-nucleoside analogs

Comb Chem High Throughput Screen. 2003 Feb;6(1):37-50. doi: 10.2174/1386207033329887.

Abstract

A combinatorial library of 60C- nucleoside analogs was synthesized by sequential coupling of building blocks followed by cyclative cleavage with DBU in an efficient manner. Only DMSO soluble compounds were tested for their modulatory effect against filarial gamma-glutamyl cysteine synthetase (gamma-GCase) and glutathione-S-transeferases (GSTs). Several compounds were found to be weak inhibitors of filarial gamma-GCase, whereas, most of them stimulated filarial GSTs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / chemistry
  • Animals
  • Bridged Bicyclo Compounds, Heterocyclic / chemistry*
  • Cattle
  • Combinatorial Chemistry Techniques / methods*
  • Filarioidea / drug effects
  • Filarioidea / enzymology
  • Glutamate-Cysteine Ligase / antagonists & inhibitors*
  • Glutathione Transferase / antagonists & inhibitors*
  • Isocyanates / chemistry
  • Nucleosides / chemical synthesis*
  • Nucleosides / pharmacology*
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / enzymology
  • Structure-Activity Relationship

Substances

  • Aldehydes
  • Bridged Bicyclo Compounds, Heterocyclic
  • Isocyanates
  • Nucleosides
  • Glutathione Transferase
  • Glutamate-Cysteine Ligase
  • 1,8-diazabicyclo(5.4.0)undec-7-ene