Prolyl Endopeptidase Inhibitors from Syzygium samarangense (Blume) Merr. & L. M. Perry

Compounds isolated from the hexane extract of the leaves of Syzygium samarangense (Blume) Merr. & L. M. Perry were tested for inhibitory activity against the following serine proteases: trypsin, thrombin and prolyl endopeptidase. The compounds were identified as an intractable mixture of α-carotene and β-carotene (1), lupeol (2), betulin (3), epi-betulinic acid (4), 2′,4′-dihydroxy-6′-methoxy-3′-methylchalcone (5), 2′-hydroxy-4′,6′-dimethoxy-3′- methylchalcone (6), 2′,4′-dihydroxy-6′-methoxy-3′,5v-dimethylchalcone (7), 2′,4′-dihydroxy- 6′-methoxy-3′-methyldihydrochalcone (8) and 7-hydroxy-5-methoxy-6,8-dimethylflavanone (9). Hydrogenation of compounds 5, 6 and 7 yielded compound 8, 2′-hydroxy-4′,6′-dimethoxy- 3′-methyldihydrochalcone (10) and 2′,4′-dihydroxy-6′-methoxy-3′,5-dimethyldihydrochalcone (11), respectively. The hydrogenated products of compounds 6 and 7 were also tested for enzyme inhibitory activity. In addition, β-sitosterol (12) and β-ᴅ-sitosterylglucoside (13) were also isolated. This is the first report of the isolation of compounds 1-6, 8 and 13 from this plant. Compounds 3-8 and 10 exhibited significant and selective inhibition against prolyl endopeptidase among three serine proteases. This is the first report of this kind of activity for all these compounds.