Unprecedented antioxidative and anti-inflammatory aryl polyketides from the brown seaweed Sargassum wightii

Abstract

Previously undescribed aryl polyketide lactones, 4-(8-ethyl-tetrahydro-7-oxo-2H-pyran-5-yl)-propyl-4′-methylbenzoate (compound 1) and methyl-2-(12-oxo-7-phenyl-8-vinyl-1-oxa-4,9-cyclododecadien-3-yl)-acetate (compound 2) were purified from ethyl acetate-methanol fraction of the brown seaweed Sargassum wightii. The structures were proposed based on their NMR and mass spectrometric data. The antioxidative activities of the lactones were significantly greater (P<0.05) (IC50 1,1-diphenyl-2-picrylhydrazyl radical scavenging 0.24–0.32mg/mL) than α-tocopherol (IC50 0.63mg/mL). The title compounds displayed considerably greater 5-lipoxygenase inhibitory activity (IC50 0.56 and 0.29mg/mL, respectively) in conjunction with higher selectivity indices (anti-cycloxygense-1IC50/anti-cycloxygense-2IC50 >1) compared to non-steroidal anti-inflammatory drugs (SIaspirin 0.03, SIibuprofen 0.43). Putative biosynthetic pathway of title polyketide products through polyketide synthase enzyme cascade catalyzed reactions substantiated the structural attributions of the hitherto unreported aryl polyketides. This is the first report of the occurrence and characterization of two rare skeletal types, oxo-2H-pyranyl and oxa-cyclododecadienyl macrolactone featuring the aryl substituent from marine organisms with potential antioxidative and anti-inflammatory activities.