title: Synthesis and evaluation of fused bispyrimidinoacridines as novel pentacyclic analogues of quadruplex-binder BRACO-19.
abstract: 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 molecular modelling. The present study also highlights that control of the pi-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 additional amino side chains, valuable in the acridine series, results here in steric perturbations of the ligand/quadruplex recognition and lowers the quadruplex/duplex selectivity.
authors.affiliation: Département Chimie Moléculaire, UMR 5250, CNRS/Université Joseph Fourier, BP 53, 38041 Grenoble cedex 9, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Debray
authors.forename: Walid
authors.initials: W
authors.lastname: Zeghida
authors.forename: Muriel
authors.initials: M
authors.lastname: Jourdan
authors.forename: David
authors.initials: D
authors.lastname: Monchaud
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Dheu-Andries
authors.forename: Pascal
authors.initials: P
authors.lastname: Dumy
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Teulade-Fichou
authors.forename: Martine
authors.initials: M
authors.lastname: Demeunynck
mesh_terms: D000166:Acridines / Q000138:chemical synthesis* / Q000737:chemistry; D054856:G-Quadruplexes; D008024:Ligands; D008958:Models, Molecular; D011743:Pyrimidines / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship
chemical_list: D000166:Acridines; D008024:Ligands; D011743:Pyrimidines; C454064:BRACO-19