Marine pyridoacridine alkaloids and synthetic analogues as antitumor agents

Pyrido[4,3,2-mn]acridines are of major interest as metabolites in sponges and ascidians. During the last few years, numerous additional compounds of this family were isolated, some of them being polycyclic structures already reported with different substituents (shermilamine or kuanoniamine-derivatives), others, such as neoamphimedine, arnoamines and styelsamines having original structures. The synthesis of these compounds and analogues have been performed in order to allow their biological evaluation. In most of the cases, the cytotoxicity of analogues was improved compared to the natural product, specially in ascididemin or meridine series. The pyridoacridines have not a sole mode of action, but it seems that the reductive DNA cleavage mediated by reactive oxygen species is a potential general mode of action.