Thesis (Ph.D.)--Chulalongkorn University, 2013

In phytochemical investigation for lipoxygenase inhibitory activity from Thai medicinal plants in the family of Dipterocarpaceae, acetone crude extract from the roots of Dipterocarpus tuberculatus was selected for isolation, purification and structure elucidation. The chromatographic separation of this crude extract led to the isolation of four new oligostilbenoids, dipterostilbenes A-D (1-4) and two stilbenoid glycosides, dipterostilbenosides A and B (14-15), were isolated together with nine known stilbenoids, diptoindonesin E (5), vaticanol B (6), trans-resveratrol (7), trans-ε-(-)-viniferin (8), cis-ε-(-)-viniferin (9), pallidol (10), α-viniferin (11), gnetin H (12) and (-)-hopeaphenol (13). The structures and relative configuration were determined on the basis of spectroscopic data as well as comparison with the previous literature data. For the structure-activity relationship study, eleven stilbenes (16-26) from Gnetum macrostachyum and two stilbenes (27-28) from Shorea roxburghii were also selected for evaluation of sbLOX-1 inhibitory activity. The results of colorimetric sbLOX-1 screening assay showed that 1, 3, 21, 24, 25 and 26 were the most active oligostilbenes. It was also found that the inhibitory activities of stilbenoids from G. macrostachyum were enhanced by the increasing number of stilbenoid monomer. However, the potency of Shorea- and Dipterocarpus-derived stilbenoids correlated with the type of oligostilbenes. The enzyme kinetic study of the inhibitory mechanisms revealed that compounds 1 and 26 were uncompetitive inhibitors, compounds 3, 21 and 25 were non-competitive inhibitor, and compound 24 were a mixed-competitive inhibitor. The inhibitory activity of 1, 3, 21, 24, 25 and 26 was not resulted from the antioxidant property and iron redox interferences as demonstrated by DPPH and 13-HPOD scavenging assays, and UV spectrophotometric and circular dichroism spectroscopic studies. Thus, the inhibitory mechanisms of these active oligostilbenoids were resulted from the enzyme inhibition without iron redox interferences or alteration of the active enzyme structure.