Benzimidazole-based small molecules as anticancer agents targeting telomeric G-quadruplex and inhibiting telomerase enzyme

Future Med Chem. 2024;16(19):2043-2067. doi: 10.1080/17568919.2024.2400982. Epub 2024 Sep 24.

Abstract

Telomeres, crucial for chromosomal integrity, have been related to aging and cancer formation, mainly through regulating G-quadruplex structures. G-quadruplexes are structural motifs that can arise as secondary structures of nucleic acids, especially in guanine-rich DNA and RNA regions. Targeting these structures by small compounds shows promise in the selective suppression of cell growth, opening up novel possibilities for anticancer treatment. A comprehensive investigation of the many structural forms of G-quadruplex ligands is required to create ground-breaking anticancer drugs. Recent research into using specific benzimidazole molecules in stabilizing telomeric DNA into G-quadruplex structures has highlighted their ability to influence oncogene expression and demonstrate antiproliferative characteristics against cancer cells. This review describes the benzimidazole derivative, designed to enhance the stability of the G-quadruplex structure DNA to suppress the activity of telomerase enzyme, exhibiting promising potential for anticancer therapy.

Keywords: Anticancer agent; DNA G-quadruplex; Ligand/small molecule interaction; Telomerase.

Plain language summary

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Publication types

  • Review

MeSH terms

  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Benzimidazoles* / chemistry
  • Benzimidazoles* / pharmacology
  • Cell Proliferation / drug effects
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • G-Quadruplexes* / drug effects
  • Humans
  • Molecular Structure
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology
  • Telomerase* / antagonists & inhibitors
  • Telomerase* / metabolism
  • Telomere* / drug effects
  • Telomere* / metabolism

Substances

  • Telomerase
  • Benzimidazoles
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Small Molecule Libraries
  • benzimidazole