These terpyridine platinum-derived G4 ligands are promising compounds for cancer treatment.
Dr. Vladimir Larionov and Dr. Natalay Kouprina both from The National Institutes of Health said, "Normal human somatic cells contain 46 chromosomes."
Telomerase/telomere-targeting therapy is considered to be a potentially promising approach for cancer treatment because even transient telomere dysfunction can induce chromosomal instability in human cells. The enzyme telomerase elongates telomeres and maintains a telomere length equilibrium that prevents telomeres from becoming critically short. In particular, formation of G4s at telomeres could impede telomerase recognition and inhibit telomere elongation leading to telomere shortening. Thus, telomeres are promising targets for discovery of ligands that stabilize G4s at telomeres, thereby perturbing telomere maintenance and leading to genomic instability.
The authors found that treatment of cancer cells with either Pt-cpym, Pt-vpym, Pt-ttpy or Pt-tpy induces telomere dysfunction leading to high levels of chromosome instability. The Larionov/Kouprina Research Team concluded in their Oncotarget Research Output, "using our dual-HAC assay we identified three terpyridine platinum compounds, Pt-tpy, Pt-vpym and Pt-cpym, that induce a high level of chromosome instability (CIN) as previously reported for the related compound Pt-ttpy. CIN observed after treatment of cells with these compounds correlates with the formation of double-stranded DNA breaks predominantly localized proximal to telomeres. The telomere-associated DNA damage induced by these drugs leads to chromatin bridge formation in late mitosis and cytokinesis. This family of G4 ligands that induce telomere dysfunction and greatly increase chromosome mis-segregation rates are promising drug candidates for treatment of cancer alone or in combination with ionizing radiation."