Ascididemin and meridine stabilise G-quadruplexes and inhibit telomerase in vitro.
Ascididemin and Meridine are two marine compounds with pyridoacridine skeletons known to exhibit interesting antitumour activities. These molecules have been reported to behave like DNA intercalators. In this study, dialysis competition assay and mass spectrometry experiments were used to determine the affinity of ascididemin and meridine for DNA structures among duplexes, triplexes, quadruplexes and single-strands. Our data confirm that ascididemin and meridine interact with DNA but also recognize triplex and quadruplex structures. These molecules exhibit a significant preference for quadruplexes over duplexes or single-strands. Meridine is a stronger quadruplex ligand and therefore a stronger telomerase inhibitor than ascididemin (IC50=11 and >80 muM, respectively in a standard TRAP assay).
Guittat
Lionel
L
Laboratoire de Biophysique, Muséum National d'Histoire Naturelle, INSERM UR 565, CNRS UMR 5153, 43 rue Cuvier, 75231 Paris cedex 05, France.
De Cian
Anne
A
Rosu
Frédéric
F
Gabelica
Valérie
V
De Pauw
Edwin
E
Delfourne
Evelyne
E
Mergny
Jean-Louis
JL
D000470:Alkaloids / Q000138:chemical synthesis / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D003956:Dialysis; D054856:G-Quadruplexes; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000378:metabolism; D008024:Ligands; D013058:Mass Spectrometry; D010618:Phenanthrolines / Q000138:chemical synthesis / Q000378:metabolism*; D011804:Quinolines / Q000138:chemical synthesis / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000470:Alkaloids; D007364:Intercalating Agents; D008024:Ligands; D010618:Phenanthrolines; D011804:Quinolines; C079196:meridine; C412046:ascididemin; D004247:DNA; D019098:Telomerase