The Dillenia suffruticosa leaves (Dilleniaceae), a folk medicine recommended in Southeast Asia for treating inflammation, were phytochemically studied for the first time and assessed for suppression of λ‐carrageenan‐induced paw oedema in rats. The crude methanolic extract orally administered at 5,000 mg/kg, displayed no toxicity and at 250 to 1,000 mg/kg significantly suppressed the paw oedema. Two‐isolated triterpenoids, betulinic acid (1) and koetjapic acid (2) orally administered at 50 mg/kg, significantly reduced the paw oedema, (p < 0.001) and (p < 0.005) at the fourth h onwards to 47.36% ± 2.23 and 53.43% ± 7.09, respectively, from 95.90% ± 6.88 oedema induced by λ‐carrageenan alone. 1 and the isolated flavonoids of vitexin (3), tiliroside (4), and kaempferol (5), displayed moderately more of cyclooxygenase (COX)‐2 than COX‐1 enzyme inhibition, whereas 2 was slightly more inhibition of COX‐1. The in silico molecular docking studies provided support to the in vitro COX studies that the isolated compounds formed H‐bonding with the amino acid residues at the COX‐2 catalytic sites. The triterpenoids were bound to the peroxidase, possibly inhibiting the peroxidase reaction, whereas the flavonoids interacted more at the cyclooxygenase, resembling celecoxib, therefore providing evidences that these compounds were responsible for the anti‐inflammatory properties of D. suffruticosa.

The crystal structure and absolute configuration of koetjapic acid were unambiguously reassigned by X-ray crystallography with strong support from NMR spectroscopic data. The acid contained 9 quaternary carbon atoms existing as an orthorhombic crystal with a space group of P2 1 2 1 2 1 and unit cell parameters of a = 7.6641(2), b = 14.6844(4) and c = 23.9316(6). Ring A adopted a chair conformation, ring B has an envelope conformation, whilst ring C assumed a halfchair and D displayed a chair conformation. The absolute configurations at C1 (R), C5 (R), C7 (S), C10 (S), C13 (R), C14 (R), C17 (S) and C18 (S) were assigned for the first time. The X-ray crystal of koetjapic acid was therefore reassigned as 3,4-seco-olean-4(23),12-diene-3,30-dioic acid. A plausible biogenetic synthetic pathway for compound 1 is also proposed.

No abstract

No abstract