The Biosynthetic Pathway of Stilbenoids from Gnetum microcarpum and SAR Study on Their PGE2 Inhibitory Activities

The biosynthesis of stilbenoid type of compounds is derived from the combination of shikimate and acetate malonate pathways. Specifically, resveratrol synthase (STS, EC 2.3.1.95) condenses three malonyl-CoA molecules and one coumaroyl-CoA molecule to form resveratrol. The oligostilbenoid compounds are mostly derived from the oligomerization of resveratrol via oxidative coupling reaction followed by several secondary reactions such as cyclization, enolization and oxidation. Stilbenoids isolated from the genus Gnetum, however, are rather small, and mainly consist of monomers and dimers. The diversity of the structure of monomers found in Gnetum other than resveratrol, also contributed to the oligomerization of oligostilbenoids isolated from the genus. This study focused on the isolation of stilbenoid compounds from Gnetum species using various chromatographic and spectroscopic techniques, together with their biosynthesis pathways, their Prostaglandin E2 inhibitory activities via radioimmunoassay method and structure-activity relationship (SAR) study. The phytochemical study on the lianas of Gnetum microcapum has led to the isolation of 11 compounds. The proposed biosynthetic pathways of the stilbenoids obtained from the plant are discussed based on literature studies. Gnetol (6) (IC50 1.84 μM) showed comparable PGE2 inhibition to that of the standard indomethacin (IC50 1.29 μM). This study demonstrated the importance of the number of hydroxyl groups and hydrophobicity in stilbenes and oligostilbenes structure for their PGE2 inhibitory activity.