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Tauropinnaic acid (25): R = NHCH2CH2S03H

Halichlorine (26)

Pinnaic acid (24) and tauropinnaic acid (25) inhibited cPLA2 activity in vitro with IC50 values of 0.2 mM and 0.09 mM, respectively. The activities of pinnaic acids were not so strong, but were still interesting, since cPLA2 inhibitors are rare.

Halichlorine, An Inhibitor of VCAM-1 Induction

Adhesion molecules are involved in the process of adhesion between cells and the extracellular matrix in the formation of multicellular bodies. The activity of adhesive molecules is very important for the maintenance of function and performance [46]. The clinical application of adhesion molecules as antiinflammatory agents and immunosuppressive agents are possible, provided that the function of the adhesive molecules can be controlled.

A simple model of multistage adhesion between leukocyte and vascular cells is proposed. This process can be classified into four stages, i.e., (1) rolling, (2) triggering, (3) strong adhesion, and (4) transmigration. VCAM-1 (vascular cell adhesion molecule-1) is affected during the phase of strong adhesion [47]. Thus, drugs that block the induced expression of VCAM-1 may be useful for treating atherosclerosis, coronary artery diseases, angina, and noncardiovascular inflammatory diseases.

Halichlorine (26) was isolated from the marine sponge Halichondria okadai Kadota [48]. Halichlorine consists of a sterically hindered 15-mem-bered lactone, an azabicyclo[4.4.0]ring, and a 5,6-spiro ring moiety. The relative stereochemistry of 26 was confirmed mainly by the coupling constants and NOESY spectral data. Furthermore, an oxidative degradation product of 26 was synthesized from D-(-)-tartaric acid to determine the absolute stereochemistry of halichlorine [49]. Halichlorine inhibits the induction of VCAM-1 at IC50 7 |xg/ml. Although VCAM-1 and ICAM (intercellular adhesion molecule 1) belong to the same immunoglobulin superfamily, halichlo-rine does not affect ICAM (IC50 > 100 |g/ml).

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