Neurotrophic Sesterterpenes Isolated from a Marine Sponge, Spongia sp.

Abstract

The MeOH extract of a marine sponge of the genus Spongia showed neurotrophic activity in pheochromocytoma (PC-12) cells.Purification of the extract afforded a new sesterterpene, deacetoxyscalarin (1), along with five known sesterterpenes (2-6).Among them, 2-6 induced neurite outgrowth in PC-12 cells at the concentration of 50 µg/mL but 1 was inactive.Marine sponges of the genus Spongia sp. are well known as rich sources of biologically active metabolites; so far the isolation of cytotoxic macrolides, 1, 2 furanoterpenes, 3 cytotoxic sesterterpenes, 4 polyhydroxylated sterols which reverse multidrug resistance, 5, 6 and aminoquinone 7 has been reported.In the course of our study on biologically active compounds from marine organisms, we also reported the isolation and structure elucidation of three new cytotoxic sesterterpenes from Spongia sp. 8 Recently, we found that the MeOH extract of the same sponge induced neurite outgrowth in pheochromocytoma (PC-12) cells.It is well known that neurons are terminally differentiated cells.Neurotrophic factors are necessary for the functional maintenance and organization of neurons.Among various neurotrophic factors, nerve growth factor (NGF) 9 has been extensively investigated and found to show pleiotrophic effects, such as the induction of neuronal differentiation, neural cell survival, and prevention of apoptosis of neurons, in both central and peripheral nervous systems. 9PC-12 cells have been used as an in vitro model system to study the mechanisms of neuronal differentiation, and NGF induces their differentiation, HETEROCYCLES, Vol.69, 2006