Unprecedented antioxidative cyclic ether from the red seaweed Kappaphycus alvarezii with anti-cyclooxygenase and lipoxidase activities

An unprecedented non-isoprenoid oxocine carboxylate cyclic ether characterised as (3S, 4R, 5S, 6Z)-3-((R)-hexan-2-yl)-3,4,5,8-tetrahydro-4-methyl-2H-oxocin-5-yl acetate was isolated from the ethyl acetate-methanol extract of the red seaweed Kappaphycus alvarezii. The structure, as well as its relative stereochemistry, was proposed on the basis of extensive spectral data. The antioxidative activity of the isolated metabolite was found to have significantly greater as determined by 1, 1-diphenyl-2-picrylhydrazyl and 2,2-azino-bis-3-ethylbenzothiozoline-6-sulfonic acid radical scavenging activities (IC50 similar to 0.3mg/mL) compared to -tocopherol (IC50>0.6mg/mL) and was comparable to the synthetic antioxidants butylated hydroxytoluene and butylated hydroxyanisole (IC50 similar to 0.35-0.34mg/mL). The compound exhibited greater activity against COX-2 (cyclooxygenase-2) than COX-1 (cyclooxygenase-1) isoform, and therefore, the selectivity index remained significantly lesser (anti-COX-1(IC50): anti-COX-2(IC50) 0.87) than synthetic anti-inflammatory drugs (0.02-0.44). No significant difference of in vivo 5-lipoxidase activity (IC50 0.95mg/mL) than ibuprofen (IC50 0.93mg/mL) indicated the potential anti-inflammatory properties of the title compound.