Naturally occurring somatostatin and vasoactive intestinal peptide inhibitors. Isolation of alkaloids from two marine sponges.

The vasoactive intestinal peptide (VIP) and somatostatin (somatotropin release inhibiting factor, SRIF) are important neurotransmitters in a number of basic physiological events. Their disturbances have been reported in many diseases such as cystic fibrosis, impotent man (VIP), Alzheimer's disease, and some tumours (SRIF). Xestospongine B (1), sceptrine (2), and ageliferine (3), three alkaloids isolated from Xestospongia sp. and Agelas novaecaledoniae are reported as somatostatin and VIP inhibitors. The natural products 1, 2 and 3 exhibited a high affinity for somatostatin (IC50 = 12 microM, 0.27 microM, and 2.2 microM, respectively), 2 and 3 showed an affinity for VIP (19.8 microM and 19.2 microM, respectively). Due to the interaction between non-peptidic compounds and somatostatin/VIP receptors, these three alkaloids could be promising agents in the research on natural non-peptidic compounds for therapeutical interventions.