Solid-Phase Synthesis of a Library Constructed of Aromatic Phosphate, Long Alkyl Chains and Tryptophane Components, and Identification of Potent Dipeptide Telomerase Inhibitors

Bioorg Med Chem Lett. 2001 Oct 8;11(19):2581-4. doi: 10.1016/s0960-894x(01)00507-8.

Abstract

Telomerase inhibitors are expected as a new candidate of therapeutic agents for cancer. Recently, we have found novel inhibitors based on the bisindole skeleton. In this study, solid-phase synthesis was applied to construct a library of inhibitors having aromatic phosphate, long alkyl chain and tryptophane components, from which a D,D-ditryptophane derivative has been identified as a new potent telomerase inhibitor with IC(50) values of 0.3 microM. A hypothetical binding model for the new inhibitors has been proposed based on the structure-activity relationship.

MeSH terms

  • Dipeptides / chemical synthesis*
  • Dipeptides / chemistry
  • Dipeptides / pharmacology
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Inhibitory Concentration 50
  • Structure-Activity Relationship
  • Telomerase / antagonists & inhibitors*
  • Tryptophan / chemistry*

Substances

  • Dipeptides
  • Enzyme Inhibitors
  • Tryptophan
  • Telomerase