title: Synthesis and cytotoxic activity of benzophenanthrolinone analogues of acronycine.
abstract: Condensation of either 2-bromobenzoic acid (4) or 2-chloro-3-nitrobenzoic acid (5) with suitable aminoquinolines 6-8 afforded phenylquinolylamines 9-13. Acid mediated cyclization gave the corresponding 12H-benzo[b][1,7]phenanthrolin-7-ones 14 and 15, and 12H-benzo[b][1,10]phenanthrolin-7-ones 16-18. Compounds 14, 16, and 17 were subsequently N-methylated to 6-demethoxyacronycine and acronycine analogues 19-21, whereas reduction of the aromatic nitro group of 18 gave the amino derivative 22. Unsubstituted 12H-benzo[b][1,10]phenanthrolin-7-ones 16, 17, 20, and 21 were devoid of significant cytotoxic activity, whereas 18 and 22, bearing a nitrogen substituent at position 11, were significantly active. Unsubstituted 12H-benzo[b][1,7]phenanthrolin-7-ones 14 and 19, which include a pyridine nitrogen in the same 4-position as the pyran oxygen of acronycine exhibited cytotoxic activities within the same range of magnitude as acronycine itself.
authors.affiliation: Laboratoire de Pharmacognosie de l'Université de Rouen-Haute Normandie, Faculté de Pharmacie, France.
authors.forename: J B
authors.initials: JB
authors.lastname: Bongui
authors.forename: A
authors.initials: A
authors.lastname: Elomri
authors.forename: E
authors.initials: E
authors.lastname: Seguin
authors.forename: F
authors.initials: F
authors.lastname: Tillequin
authors.forename: B
authors.initials: B
authors.lastname: Pfeiffer
authors.forename: P
authors.initials: P
authors.lastname: Renard
authors.forename: A
authors.initials: A
authors.lastname: Pierré
authors.forename: G
authors.initials: G
authors.lastname: Atassi
mesh_terms: D000175:Acronine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D007939:Leukemia L1210 / Q000188:drug therapy; D013058:Mass Spectrometry; D051379:Mice; D010618:Phenanthrolines / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007202:Indicators and Reagents; D010618:Phenanthrolines; D000175:Acronine