Marine pyridoacridine alkaloids and synthetic analogues as antitumor agents

Abstract

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.

Short Total Synthesis of the Marine Alkaloid Subarine

“…Among the numerous types of compounds isolated from tunicates, the pyridoacridone type alkaloids [2,3] have attended greatest interest, due to their significant cytotoxic activities [1,4,5].…”

“…2009; 77; 1-7. A first total synthesis of subarine (2) has been published by the Delfourne group [5], but this synthesis requires multistep synthesis of the central intermediates, and no information about biological activities is given in this publication.…”

Ascididemin and meridine stabilise G-quadruplexes and inhibit telomerase in vitro

“…Several marine-derived metabolites have reached clinical trials as antitumour agents. Among marine alkaloids, the pyridoacridines seem to be the largest group, with most of the compounds being isolated from sponges and runicates (for a review, see [1]). In 1991, Schmitz et al [2] described the isolation and structure of meridine (Fig.…”

Alkaloids from Marine Invertebrates as Important Leads for Anticancer Drugs Discovery and Development

“…[102]. Since then, more than 80 pyridoacridines have been found in many marine organisms such as sponges, tunicates, anemones, and mollusks [100,103,104]. Most pyridoacridines have been reported to have significant cytotoxicity due to a highly planar electron-deficient aromatic ring system that can intercalate DNA, resulting in the inhibition of cell growth [105].…”