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.
Keywords: Metal complex, benzimidazole, disulfide, FRET, circular dichroism, quadruplex DNA.
Graphical Abstract
Anti-Cancer Agents in Medicinal Chemistry
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.
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Saour Kawkab and Lafta Dunya, Synthesis of New Benzimidazole and Benzothiazole Disulfide Metal Complexes as G-quadruplex Binding Ligands, Anti-Cancer Agents in Medicinal Chemistry 2016; 16 (7) . https://dx.doi.org/10.2174/1871520616666160204111637
DOI https://dx.doi.org/10.2174/1871520616666160204111637 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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