To investigate the relationship between the structures of methylhesperetin-7-alkyl
ether analogues and their anti-inflammatory activities, nine new compounds, methyl-
hesperetin (2), methylhesperetin-7-ethyl
ether (3), 7-n-butyl
ether (4), 7-n-hexyl
ether (5), 7-n-octyl
ether (6), 7-n-decyl
ether (7), 7-n-dodecyl
ether (8), 7-n-tetradecyl
ether (9) and 7-n-hexadecyl
ether (10), were synthesized with the lead compound of
methylhesperidin (1). Their structures were confirmed by UV, 1H NMR, MS and HR-MS spectral data. The in vivo antiinflammatory activities of these compounds were tested on mouse paw
edema induced by Freund's complete adjuvant (FCA) and mouse capillary permeability induced by
acetic acid with po dose of 300 mg x kg(-1) x d(-1). The result indicated that the anti-inflammatory activities of the synthetic compounds increased firstly and then decreased with the elongating of the length of alkyl chain. After 25-day
oral administration of compounds 6, 7 and 8, the inhibitory rates on mouse paw
edema of
adjuvant arthritis (AA) were 31.9%, 38.5%, 39.1%, respectively. They showed the concentrations of COX-2 in serum of AA mice respectively were 79.3, 75.4, 73.9 ng x L(-1) and the concentrations of
PGE2 were in correspondence with 275.4, 258.9, 242.6 ng x L(-1). The inhibitory rates of compounds 6 and 7 on mouse capillary permeability induced by
acetic acid were, respectively, 42.4% and 41.5% after 5-day
oral administration. Compared with the lead compound of
methylhesperidin, the anti-inflammatory activities of compounds 6, 7 and 8 were increased and showed an effective inhibition on the symptom of
adjuvant arthritis and capillary permeability in mice.