Novel imidazo[1,2-a]naphthyridinic systems (part 1): synthesis, antiproliferative and DNA-intercalating activities.
Novel imidazo[1,2-a]naphthyridinic systems 6a-15a and 6b-15b were obtained from Friedländer'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.
Andaloussi
Mounir
M
Univ Clermont 1, UFR Pharmacie, Clermont-Ferrand F-63001, France.
Moreau
Emmanuel
E
Masurier
Nicolas
N
Lacroix
Jacques
J
Gaudreault
René C
RC
Chezal
Jean-Michel
JM
El Laghdach
Anas
A
Canitrot
Damien
D
Debiton
Eric
E
Teulade
Jean-Claude
JC
Chavignon
Olivier
O
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry*; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D007364:Intercalating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D007093:Imidazoles; D007364:Intercalating Agents; D009287:Naphthyridines; C029899:imidazole; D004247:DNA