A photochemical approach to pyridopyrroloquinoline derivatives as new potential anticancer agents.
Indoloquinoline alkaloid cryptolepine and pyridocarbazole alkaloid ellipticine are of great interest because in vitro and in vivo studies revealed their good cytotoxic properties. In order to obtain some biologically active analogs of these compounds, we developped a synthesis based on the photocyclisation of tertiary N-methylated enaminones derived from cyclopentane-1,3-dione and 3 or 6-aminoquinoline. The angular cyclised compounds thus obtained were submitted to Beckmann rearrangement, preceded by the formation of a Z oxime. Finally, the delta-lactame ring was oxidized using 10% palladium/carbon in diphenylether and pyridopyrroloquinolines were obtained. These compounds and the intermediate lactams and cyclopentanopyrroloquinolines were tested in vitro on K 562 cells and A 2780 doxorubicine sensitive and resistant cells. All compounds were less effective than doxorubicine in sensitive cells but their activity wasn't decreased by MDR resistance.
Aragon
Pierre-Jean
PJ
Laboratoire de Chimie Organique Pharmaceutique, E.A. 2414, Faculté de Pharmacie, 15 avenue Clarles Flahault, 34060 Montpellier, France.
Yapi
Ange-Désiré
AD
Pinguet
Frédéric
F
Chezal
Jean-Michel
JM
Teulade
Jean-Claude
JC
Chapat
Jean-Pierre
JP
Blache
Yves
Y
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D006801:Humans; D010777:Photochemistry / Q000379:methods*; D011728:Pyridones / Q000737:chemistry* / Q000494:pharmacology; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D011728:Pyridones; D011804:Quinolines