93533-59-6Relevant articles and documents
Imidazonaphthyridine systems (part 2): Functionalization of the phenyl ring linked to the pyridine pharmacophore and its replacement by a pyridinone ring produces intriguing differences in cytocidal activity
Masurier, Nicolas,Debiton, Eric,Jacquemet, Alicia,Bussière, Antoine,Chezal, Jean-Michel,Ollivier, Anthony,Tétégan, Daté,Andaloussi, Mounir,Galmier, Marie-Joseph,Lacroix, Jacques,Canitrot, Damien,Teulade, Jean-Claude,Gaudreault, René C.,Chavignon, Olivier,Moreau, Emmanuel
experimental part, p. 137 - 150 (2012/07/16)
We recently discovered that five- and pseudo-five-fused-ring derivatives in an imidazonaphthyridine series were promising hit compounds for the development of new DNA-intercalators. In this study, novel (dihydro)imidazo[1,6] and [1,7]naphthyridi(no)nes were prepared including pseudo-pentacycles. All the compounds synthesized were screened against four tumor cell lines. Compounds 3(b-d) showed significant in vitro cytotoxicity, and DNA intercalation properties were demonstrated at 25 μM. Imidazonaphthyridinones exhibited no DNA binding affinity despite significant growth inhibition activity. Interestingly, when a pyridinone pharmacophore was linked to the imidazo[1,2-a]pyridine scaffold, the geometric orientation of the link had a strong impact on the growth inhibition activity. From these results we conclude that the moderate cytotoxicity observed for these compounds is independent of their DNA-binding and topoisomerase inhibition activities.
