Structure-activity relationships among guanine-quadruplex telomerase inhibitors

Pharmacol Ther. 2000 Mar;85(3):133-9. doi: 10.1016/s0163-7258(99)00065-0.

Abstract

The ribonucleoprotein telomerase is responsible for maintaining the length of telomeric ends of chromosomes in tumour cells. It is activated in over 85% of the tumour cells, and is emerging as a major target for cancer chemotherapy. A range of molecules containing tricyclic and tetracyclic aromatic chromophores has been shown to inhibit the telomerase enzyme system at the micromolar level. There is evidence that they do so via stabilisation of a guanine-quadruplex structure, which provides a stop signal for further telomere elongation. The known structure-activity relationships for these compounds are summarised, and pointers for the development of future molecules with enhanced selectivity are described.

Publication types

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

MeSH terms

  • Binding Sites
  • Cell Transformation, Neoplastic
  • DNA / chemistry
  • DNA / metabolism*
  • Guanine / chemistry
  • Guanine / metabolism*
  • Humans
  • Ligands
  • Models, Molecular
  • Nucleic Acid Conformation
  • Structure-Activity Relationship
  • Telomerase / antagonists & inhibitors*
  • Telomerase / metabolism
  • Telomere / physiology

Substances

  • Ligands
  • Guanine
  • DNA
  • Telomerase