Previously undescribed antioxidative azocinyl morpholinone alkaloid from red seaweed <i>Gracilaria opuntia</i> with anti-cyclooxygenase and lipoxygenase properties

Abstract

In vitro antioxidative and anti-inflammatory bioassay-guided fractionation of the methanol: ethyl acetate crude extract of the thalli of red seaweed Gracilaria opuntia collected from the Gulf of Mannar led to the isolation of a new morpholine alkaloid 3-(2-ethyl-6-((3Z,7Z)-1,2,5,6-tetrahydroazocin-5-yl)hexyl) morpholin-6-one. The substituted azocinyl morpholinone recorded significant 1,1-diphenyl-2-picryl-hydrazil free radical scavenging activities (IC50 ~ 0.086 mg/mL) compared to the commercially available antioxidants, butylated hydroxyanisole, butylated hydroxytoluene, and α-tocopherol (IC50 > 0.20 mg/mL). The title compound showed greater cyclooxygenase-2 (COX-2) inhibitory activity (IC50 0.84 mg/mL) in conjunction with in vitro 5-lipoxidase inhibitory activity (IC50 0.85 mg/mL) than non-steroidal anti-inflammatory drugs (NSAIDs). The test compound had better selectivity index (COX-1/COX-2 ratio) (1.17 mg/mL) compared to aspirin (0.02 mg/mL), Na salicylate (0.73 mg/mL) and ibuprofen (0.44 mg/mL). The animals challenged with the substituted azocinyl morpholinone significantly mitigated the carrageenan-induced paw edema in time-dependent manner till the end of 6 h.