Discovery of Anti-Inflammatory Alkaloids from Sponge Suggests New Biosynthetic Pathways for Pyrrole-Imidazole Alkaloids.

Pyrrole-imidazole alkaloids (PIAs) are a class of marine sponge derived natural products which have complex carbon frameworks and broad bioactivities. In this study, four new alkaloids, stylimassalins A-B (-), , and , together with two known compounds ( and ), were isolated from . Compounds , , and are the C-2 brominated analogues of , , and , respectively. Their structures display three different scaffolds, of which scaffold 1 (compounds ,) is new. A new biosynthetic pathway from oroidin, through spongiacidin, to latonduine and scaffold 1 was proposed by our group, in which the C12-N13-cleavaged compounds of spongiacidin (scaffold 2), dubbed seco-spongiacidins ( and ), are recognized as a key bridged scaffold, to afford PIA analogues (, and ,). An anti-inflammatory evaluation in a zebrafish inflammation model induced by copper sulphate (CuSO) demonstrated that stylimassalins A and B ( and ) could serve as a promising lead scaffold for treating inflammation.