Design, synthesis and evaluation of potent thymidylate synthase X inhibitors

Bioorg Med Chem Lett. 2008 Jun 15;18(12):3628-31. doi: 10.1016/j.bmcl.2008.04.080. Epub 2008 May 6.

Abstract

Three synthesized series of compounds based on a thiazolidine core allowed identification of potent inhibitors of thymidylate synthase X. The evaluation of the catalytic activity of the enzyme in the presence of these molecules revealed two distinct classes of compounds that inhibit ThyX with submicromolar concentrations, which could lead, after optimization, to effective inhibitors with potential biomedical interest.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Design
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Molecular Conformation
  • Stereoisomerism
  • Structure-Activity Relationship
  • Thiazolidines / chemical synthesis*
  • Thiazolidines / chemistry
  • Thiazolidines / pharmacology*
  • Thymidylate Synthase / antagonists & inhibitors*
  • Thymidylate Synthase / chemistry
  • Time Factors

Substances

  • Enzyme Inhibitors
  • Thiazolidines
  • Thymidylate Synthase