Synthesis and cytotoxic activity of benzophenanthrolinone analogues of acronycine.
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.
Bongui
J B
JB
Laboratoire de Pharmacognosie de l'Université de Rouen-Haute Normandie, Faculté de Pharmacie, France.
Elomri
A
A
Seguin
E
E
Tillequin
F
F
Pfeiffer
B
B
Renard
P
P
Pierré
A
A
Atassi
G
G
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*
D000972:Antineoplastic Agents, Phytogenic; D007202:Indicators and Reagents; D010618:Phenanthrolines; D000175:Acronine