Synthesis and cytotoxic evaluation of analogues of the marine pyridoacridine amphimedine.
4-Substituted-7H-pyrido-[4,3,2-de][1,8] or [1,9]-phenanthroline-7-ones and 9-methyl-1,4-diazanaphtacene-3,10-dione, analogues of the marine pyridoacridine amphimedine were synthesised from isoquinoline-5,8-dione. The first compounds were obtained starting from a Diels-Alder reaction whereas the synthesis of the last compound was initiated by a reaction of condensation with 2-aminoacetophenone. The different tetra- and pentacyclic compounds were evaluated for in vitro cytotoxic activities against six distinct human cancer cell lines. All the compounds exhibit cytotoxic activity with IC(50) values (i.e., the drug concentration inhibiting the mean growth value of the six cell lines by 50%)<10(-7)M for two of them.
Brahic
Christine
C
Centre de Phytopharmacie, UMR-CNRS 5054, Université de Perpignan, 52 Avenue de Villeneuve, 66860 Perpignan Cedex, France.
Darro
Francis
F
Belloir
Mirabelle
M
Bastide
Jean
J
Kiss
Robert
R
Delfourne
Evelyne
E
D000166:Acridines / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001372:Aza Compounds; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007546:Isoquinolines; D009682:Magnetic Resonance Spectroscopy; D010618:Phenanthrolines / Q000138:chemical synthesis / Q000494:pharmacology; D011161:Porifera / Q000737:chemistry; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000166:Acridines; D001372:Aza Compounds; D007546:Isoquinolines; D010618:Phenanthrolines; C475900:pyridoacridine; C475901:amphimedine