Abstract
A series of quassinoids were observed to be potent inhibitors of induced inflammation and arthritis in rodents. Brusatol afforded the most potent activity followed by brucein-D. A 3-hydroxy-Δ3-2-oxo moiety in brusatol or a 1-hydroxy-Δ3-2-oxo moiety in brucein-D, as well as a C-15 ester-bearing δ-lactone ring in brusatol and C-11 and C-12 free hydroxyl groups are required in both quassinoids for potent anti-inflammatory activity. Preliminary studies indicate that one of the modes of action of quassinoids as anti-inflammatory agents is to stabilize lysosomal membranes, reducing the release of hydrolytic enzymes that cause damage to surrounding tissues.
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