1093239-93-0Relevant academic research and scientific papers
Novel imidazo[1,2-a]naphthyridinic systems (part 1): Synthesis, antiproliferative and DNA-intercalating activities
Andaloussi, Mounir,Moreau, Emmanuel,Masurier, Nicolas,Lacroix, Jacques,Gaudreault, Rene C.,Chezal, Jean-Michel,El Laghdach, Anas,Canitrot, Damien,Debiton, Eric,Teulade, Jean-Claude,Chavignon, Olivier
, p. 2505 - 2517 (2008)
Novel imidazo[1,2-a]naphthyridinic systems 6a-15a and 6b-15b were obtained from Friedlaender's reaction in imidazo[1,2-a]pyridine series. Most of the compounds were evaluated for their antitumor activity in the NCIs in vitro human tumor cell line screening panel. Among them, pentacyclic derivatives 13b and 14a exhibited in vitro activity comparable to anticancer agent such as amsacrine. Their mechanism of cytotoxicity action was unrelated to poisoning or inhibiting abilities against topo1. On the contrary, we highlighted a direct intercalation of the drugs into DNA by electrophoresis on agarose gel.
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.
