Title:Synthesis of New Benzimidazole and Benzothiazole Disulfide Metal Complexes as G-quadruplex Binding Ligands
Volume: 16
Issue: 7
Author(s): Kawkab Saour and Dunya Lafta
Affiliation:
Keywords:
Metal complex, benzimidazole, disulfide, FRET, circular dichroism, quadruplex DNA.
Abstract: Compounds that can bind and stabilize non-canonical DNA structures are named quadruplex and are of
interest in anticancer drug design due to their selective inhibitions of telomerase and consequent effects on cell
proliferation. In this study, we report novel Co/Cu [II] complex compounds as G-quadruplex DNA binding
ligands. The results from the preliminary assay indicated that the introduction of a positively charged 6-membered
tail to the aromatic terminal group of benzimidazole significantly enhanced the binding affinity with the
quadruplex and exhibited anti-telomerase activity. These derivatives showed significant selectivities for the
telomeric quadruplex over duplex nucleic acids. The stabilization of non-canonical forms estimated with the FRET
DNA technology using different sequences, such as F21T, c-kit1 and c-kit2, in cancer cell lines were assessed.
Three members of this family showed to be very selective in stabilizing one particular G-quadruplex.
