title: Synthesis of 6-dialkylaminoalkylamino pyrano[2,3-c]acridones and benzo[b]pyrano[3,2-h]acridones: soluble acronycine analogues with increased cytotoxic activity.
abstract: 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.
authors.affiliation: 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.
authors.forename: Nadine
authors.initials: N
authors.lastname: Costes
authors.forename: Abdelhakim
authors.initials: A
authors.lastname: Elomri
authors.forename: Hanh
authors.initials: H
authors.lastname: Dufat
authors.forename: Sylvie
authors.initials: S
authors.lastname: Michel
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Seguin
authors.forename: Michel
authors.initials: M
authors.lastname: Koch
authors.forename: François
authors.initials: F
authors.lastname: Tillequin
authors.forename: Bruno
authors.initials: B
authors.lastname: Pfeiffer
authors.forename: Pierre
authors.initials: P
authors.lastname: Renard
authors.forename: Stéphane
authors.initials: S
authors.lastname: Léonce
authors.forename: Alain
authors.initials: A
authors.lastname: Pierré
mesh_terms: 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
chemical_list: D000166:Acridines; D000175:Acronine