Synthesis of 6-dialkylaminoalkylamino pyrano[2,3-c]acridones and benzo[b]pyrano[3,2-h]acridones: soluble acronycine analogues with increased cytotoxic activity.
The novel 6-dialkylaminoalkylamino-3,3,12-trimethyl-3,12-dihydro-7H-pyrano[2,3-c]acridine-7-ones 5-11 and their benzo [b]pyrano[2,3-h]acridine-7-one counterparts 12-18 were prepared by treatment of acronycine (1) or benzo[b]acronycine (4) with an excess of the appropriate dialkylaminoalkylamine. In both series, the introduction of a dialkylaminoalkylamino side chain at position 6 resulted in a significant increase of the cytotoxic activity against L1210 cells when compared with the parent compounds bearing a methoxy group, accompanied with an increased potency to arrest cells in the G2 + M phases of the cell cycle.
Costes
Nadine
N
Laboratoire de Pharmacognosie de l'Université René Descartes, UMR/CNRS No. 8638, Faculté des Sciences Pharmaceutiques et Biologiques, 4, Avenue de l'Observatoire, F-75006 Paris, France.
Elomri
Abdelhakim
A
Dufat
Hanh
H
Michel
Sylvie
S
Seguin
Elisabeth
E
Koch
Michel
M
Tillequin
François
F
Pfeiffer
Bruno
B
Renard
Pierre
P
Léonce
Stéphane
S
Pierré
Alain
A
D000166:Acridines / Q000138:chemical synthesis* / Q000633:toxicity*; D000175:Acronine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000633:toxicity*; D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D051379:Mice; D012995:Solubility; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000502:physiology
D000166:Acridines; D000175:Acronine