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Design, synthesis, biophysical and biological studies of trisubstituted naphthalimides as G-quadruplex ligands
- Source :
-
Bioorganic & Medicinal Chemistry . Nov2011, Vol. 19 Issue 21, p6419-6429. 11p. - Publication Year :
- 2011
-
Abstract
- Abstract: A series of trisubstituted naphthalimides have been synthesized and evaluated as telomeric G-quadruplex ligands by biophysical methods. Affinity for telomeric G-quadruplex AGGG(TTAGGG)3 binding was first screened by fluorescence titrations. Subsequently, the interaction of the telomeric G-quadruplex with compounds showing the best affinity has been studied by isothermal titration calorimetry and UV-melting experiments. The two best compounds of the series tightly bind the telomeric quadruplex with a 2:1 drug/DNA stoichiometry. These derivatives have been further evaluated for their ability to inhibit telomerase by a TRAP assay and their pharmacological properties by treating melanoma (M14) and human lung cancer (A549) cell lines with increasing drug concentrations. A dose-dependent inhibition of cell proliferation was observed for all cellular lines during short-term treatment. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 09680896
- Volume :
- 19
- Issue :
- 21
- Database :
- Academic Search Index
- Journal :
- Bioorganic & Medicinal Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 66661959
- Full Text :
- https://doi.org/10.1016/j.bmc.2011.08.062