Synthesis and evaluation of fused bispyrimidinoacridines as novel pentacyclic analogues of quadruplex-binder BRACO-19.
The present article reports on the design and the synthesis of a series of mono- and bis-pyrimidinoacridines and their evaluation as a novel family of quadruplex-binders. It is shown that bispyrimidinoacridines represent an interesting compromise between easy synthetic access and efficiency in terms of quadruplex interaction (both affinic and selective), as judged by G4-FID assay and mol. modeling. The present study also highlights that control of the $π$-stacking interactions taking place between the ligand and the accessible G-tetrad of a quadruplex-DNA is indeed essential for good recognition but not exclusively (key role of direct and water-mediated H-bonds). The introduction of addnl. amino side chains, valuable in the acridine series, results here in steric perturbations of the ligand/quadruplex recognition and lowers the quadruplex/duplex selectivity. [on SciFinder(R)]
Références
- Titre
- Synthesis and evaluation of fused bispyrimidinoacridines as novel pentacyclic analogues of quadruplex-binder BRACO-19.
- Type de publication
- Article de revue
- Année de publication
- 2009
- Auteurs
- Debray, Julien, Zeghida Walid, Jourdan Muriel, Monchaud David, Dheu-Andries Marie-Louise, Dumy Pascal, Teulade-Fichou Marie-Paule, and Demeunynck Martine
- Revue
- Org. Biomol. Chem.
- Volume
- 7
- Pagination
- 5219–5228
- ISSN
- 1477-0520
- DOI
- 10.1039/b912716j
Soumis le 12 avril 2018