Marine organisms are a rich source for natural products. Pyrrolo[4,3, 2-de]
quinolines and pyrido[4,3,2-mn]
acridines are of major interest as metabolites in sponges and ascidians. Many of these compounds have generated interest both as challenging problems for structure elucidation and synthesis as well as for their cytotoxicities. The isolation, structure proof,
biological activities, chemical properties and synthesis have attracted the attention of chemists, biologists and pharmacists. The principal structural feature of these
alkaloids is the core of a planar
iminoquinone moiety which can intercalate into
DNA and cleave the
DNA double helix or inhibit the action of
topoisomerase II. Of the makaluvamines,
makaluvamine F and A are the most cytotoxic to the HCT 116 cell line. The enhanced toxicity of the makaluvamines towards xrs-6 cells shows that all of the makaluvamines, except makaluvamine B, act like
m-AMSA and
etoposide in inhibiting
topo iso merases via cleavable complex formation, or via the direct induction of
DNA double-strand breaks. They are also amongst the most potent inhibitors of
topoisomerase II. Both
makaluvamine A and C can decrease
tumor size in a solid human
tumor model.
Discorhabdin A and C in contrast are of high cytotoxicity, but they exhibit no inhibition of
topoisomerase II. As representatives of the derivatives of pyrido[4,3,2-mn]
acridine, cystodytins, kuanoniamines and diplamine are the most potent to inhibit HCT replication.
Eilatin, as a
1,10-phenanthroline derivative, can form complexes with
metal ions. It has been shown that these
metal complexes can bind to
DNA by intercalation. The new members of the pyrrolo[4,3,2-de]
quinolines and pyrido[4,3, 2-mn]
acridines, such as veiutamine, discorhabdin G, tsitsikammamines, epinartins, arnoamines as well as sagitol are reviewed. Some successful syntheses of pyrrolo[4,3,2-de]
quinoline ring system and pyrido[4,3,2-mn]
acridine ring system are also reviewed in this article.