Previously undescribed benzoxepins with bioactivities against inducible pro-inflammatory cyclooxygenase and lipoxygenase from Rhizophora annamalayana Kathir.

Two unprecedented benzoxepins were obtained from the ethyl acetate fraction of the leaves of Rhizophora annamalayana Kathir, and characterized as 4-(11-(hydroxymethyl)-10-methylpentan-2-yl)-4, 5-dihydrobenzo[c]oxepin-1(3H)-one (1) and (E)-methyl-14-hydroxy-4-(11-(5-hydroxy-1-oxo-3,4,5-tetrahydrobenzo[c]oxepin-4-yl)ethyl)-10-methylhept-11-enoate (2). The benzoxepin 2 exhibited greater 1, 1-diphenyl-2-picrylhydrazyl and 2, 2'-azino-bis-3 ethylbenzothiozoline-6-sulfonic acid diammonium radical scavenging assays (IC50 0.68 and 0.84 mg/mL, respectively) than those recorded with 1 (IC50 0.70 and 0.89 mg/mL, respectively). The tetrahydrobenzo[c]oxepin analogue (2) exhibited significantly great cyclooxygenase-2 and 5-lipoxygenase inhibitory properties (IC50 0.87 and 0.94 mg/mL, respectively), while compared with its dihydrobenzo[c]oxepin-1(3H)-one isoform (1) (IC50 1.16 and 1.64 mg/mL, respectively). The dihydrobenzo[c]oxepin-1(3H)-one isoform (2) exhibited significantly greater selectivity index (~2) than synthetic ibuprofen (0.44) (p < 0.05), which attributed the higher anti-inflammatory selectivity of the former against inducible pro-inflammatory cyclooxygenase-2 than its constitutive isoform (cyclooxygenase-1). No significant difference in 5-lipoxygenase (5-LOX) inhibitory activities were apparent between compound 2 (IC50 0.94 mg/mL) and synthetic ibuprofen (IC50 0.93 mg/mL).