In our continuing search for biologically active substances from marine organisms, three novel alkaloids halichlorine (1), pinnaic acid (2) and norzoanthamine (4) were isolated. The structures of these alkaloids were elucidated mainly by detailed analysis of NMR data and MS spectral data. Halichlorine (1) was isolated from the marine sponge Halichondria okadai Kadota. This compound inhibits the induction of VCAM-1 (vascular cell adhesion molecule-1) at IC_<50> 7μg/ml. Drugs that block the induced expression of VCAM-1 may be useful for treating atherosclerosis, coronary artery diseases, angina and noncardiovascular inflammatory diseases. We report here the isolation and structural elucidation of 1. A cytosolic 85-kDa phospholipase (cPLA_2) exhibits specificity for the release of arachidonic acid from membrane phospholipids. Therefore, compounds that inhibit cPLA_2 activity have been targeted as anti-inflammatory agents. Pinnaic acid (2) isolated from the Okinawan bivalve Pinna muricata, inhibits the cPLA_2 activity at 0.2mM. Interestingly, the structure of 1 is closely related to that of 2. Therefore, each carbon atom has been tentatively numbered under biogenetic consideration of formation of the N-C23 bond. Further studies on chemistry of halichlorine, including its absolute configuration, biogenetic pathway and structure-activity relationships, are currently in progress in our laboratory. Biogenetic pathway of zoanthamine and norzoanthamines (4) exhibiting inhibitory effect of IL-6 production will be described here.
