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 IC50 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. (C) 2002 Elsevier Science Ltd. All rights reserved.