Synthesis and biological evaluation of indoloquinolines and pyridocarbazoles: a new example of unexpected photoreduction accompanying photocyclization.
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 developed a synthesis based on the photocyclization of tertiary N-substituted enaminones derived from 1,3-cyclohexandione and 3 or 6-aminoquinoline. The angular cyclized compounds thus obtained were tested in vitro on K 562 cells and A 2780 doxorubicin sensitive and resistant cells. All compounds were less effective than doxorubicin in sensitive cells but their activity wasn't decreased by MDR resistance.
Aragon
Pierre-Jean
PJ
Laboratoire de Chimie Organique Pharmaceutique, EA 2414, Faculté de Pharmacie, Montpellier, France.
Yapi
Ange-Désiré
AD
Pinguet
Frédéric
F
Chezal
Jean-Michel
JM
Teulade
Jean-Claude
JC
Blache
Yves
Y
D000470:Alkaloids / Q000138:chemical synthesis* / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003500:Cyclization; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004611:Ellipticines / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D020014:K562 Cells; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D010777:Photochemistry; D014466:Ultraviolet Rays