Advances in the molecular design of potential anticancer agents via targeting of human telomeric DNA

Chem Commun (Camb). 2014 Jun 21;50(49):6422-38. doi: 10.1039/c4cc00611a. Epub 2014 Apr 3.

Abstract

Telomerases are an attractive drug target to develop new generation drugs against cancer. A telomere appears from the chromosomal termini and protects it from double-stranded DNA degradation. A short telomere promotes genomic instability, like end-to-end fusion and regulates the over-expression of the telomere repairing enzyme, telomerase. The telomerase maintains the telomere length, which may lead to genetically abnormal situations, leading to cancer. Thus, the design and synthesis of an efficient telomerase inhibitor is a viable strategy toward anticancer drugs development. Accordingly, small molecule induced stabilization of the G-quadruplex structure, formed by the human telomeric DNA, is an area of contemporary scientific art. Several such compounds efficiently stabilize the G-quadruplex forms of nucleic acids, which often leads to telomerase inhibition. This Feature article presents the discovery and development of the telomere structure, function and evolution in telomere targeted anticancer drug design and incorporates the recent advances in this area, in addition to discussing the advantages and disadvantages in the methods, and prospects for the future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • DNA Probes / chemistry
  • DNA Probes / metabolism
  • Drug Design
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / metabolism
  • G-Quadruplexes* / drug effects
  • Genomic Instability
  • Humans
  • Ligands
  • Molecular Dynamics Simulation
  • Telomerase / antagonists & inhibitors*
  • Telomerase / metabolism
  • Telomere / chemistry
  • Telomere / metabolism*

Substances

  • Antineoplastic Agents
  • DNA Probes
  • Enzyme Inhibitors
  • Fluorescent Dyes
  • Ligands
  • Telomerase