3-Methyl-4,5-dihydro-oxepine, polyoxygenated seco-cyclohexenes and cyclohexenes from Uvaria flexuosa and their anti-inflammatory activity

The phytochemical investigation of the methanolic extract of Uvaria flexuosa (Annonaceae) leaves led to the isolation of seven compounds including, 3-methyl-4,5-dihydro-oxepine (flexuvaroxepine A), four polyoxygenated seco-cyclohexene (flexuvarin A-D) and two polyoxygenated cyclohexene (flexuvarol A-B) derivatives, together with four known flavones. The structures of the isolated compounds were elucidated using different spectroscopic techniques. A plausible biogenetic route of the new compounds was discussed. The anti-inflammatory activity of the isolated compounds was evaluated by superoxide anion generation and elastase release assays. Among the tested compounds, flexuvarol B and chrysin showed the most potent anti-inflammatory effect by inhibiting superoxide anion generation and elastase release from human neutrophils in response to fMLP with IC₅₀ 2.25-5.55 μM. Moreover, 5-hydroxy-6,7-dimethoxy-flavone showed selective inhibitory activity on superoxide anion generation (IC₅₀ = 1.19 ± 0.34 μM).