Previously undescribed antioxidative azocinyl morpholinone alkaloid from red seaweed Gracilaria opuntia with anti-cyclooxygenase and lipoxygenase properties.

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.

Highly oxygenated antioxidative 2H-chromen derivative from the red seaweed Gracilaria opuntia with pro-inflammatory cyclooxygenase and lipoxygenase inhibitory properties.

Phytochemical investigation of the thalli of ethyl acetate-methanol extract of the red seaweed Gracilaria opuntia led to isolation of a substituted 2H-chromen derivative of unusual structure possessing highly oxygenated carbon skeleton, characterised as 2-acetoxy-2-(5-acetoxy-4-methyl-2-oxotetrahydro-2H-pyran-4-yl)ethyl 4-(3-methoxy-2-(methoxymethyl)-7-methyl-3,4,4a,7,8,8a-hexahydro-2H-chromen-4-yloxy)-5-methylheptanoate, which have not been reported in nature. The chemical structure was resolved by detailed spectroscopic analysis. The anti-inflammatory activity of the newly reported metabolite was determined by pro-inflammatory cyclooxygenase and 5-lipoxygenase inhibitory assays. The anti-inflammatory selectivity index of the title compound recorded greater value (SI: anti-cycloxygense- 1IC50 /anti-cycloxygense- 2IC50  ~ 1.26) than synthetic NSAIDs (aspirin and ibuprofen, SI: 0.02 and 0.44, respectively), and consequently, appeared to be safer. The antioxidative activity of the title compound was significantly greater as determined by 2, 2-diphenyl-1-picrylhydrazyl and 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) radical scavenging activities (IC50 0.26-0.32 mg/mL) compared to α-tocopherol (IC50 > 0.6 mg/mL), and was comparable to the synthetic antioxidants butylated hydroxytoluene and butylated hydroxyanisole (IC50 ~ 0.25-0.34 mg/mL).

Antioxidative sulphated polygalactans from marine macroalgae as angiotensin-I converting enzyme inhibitors.

Antioxidant and antihypertensive potential of the sulphated polygalactans isolated from the marine macroalgae Kappaphycus alvarezii and Gracilaria opuntia were assessed by utilising different in vitro systems. The galactans isolated from K. alvarezii possessed significantly greater antioxidative properties as determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH IC90 0.97 mg/mL) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS.+ IC90 0.72 mg/mL) scavenging activities than those isolated from G. opuntia (DPPH IC90 1.2 mg/mL and ABTS 0.86 mg/mL). The sulphated polygalactan →4)-4-O-sulphonato-(2-O-methyl)-ß-D-galactopyranosyl-(1→4)-3,6-anhydro-(2-O-methyl)-α-D-galactopyranan from K. alvarezii showed greater angiotensin-I-converting enzyme (ACE) inhibitory activity (IC50 0.02 µg/mL) than →3)-4-O-sulphonato-(6-O-acetyl)-ß-D-galactopyranosyl-(1→4)-3,6-anhydro-(2-O-sulphonato)-α-D-galactopyranosyl-(1→3)-4-O-sulphonato-(6-O-acetyl)-ß-D-xylosyl-(1→3)-4-O-sulphonato-(6-O-acetyl)-ß-D-galactopyranosyl-(1→4)-3,6-anhydro-(2-O-sulphonato)-α-D-galactopyranan motif extracted from G. opuntia (IC50 0.70 µg/mL). Structure activity correlation studies displayed that the ACE inhibitory properties of titled polygalactans were directly proportional to their electronic properties and inversely with the steric and hydrophobic characteristics. Putative ACE inhibitory mechanism of action of sulphated galactans from marine macroalgae corroborated the structure bioactivity correlation analysis.

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 ~ 0.3 mg/mL) compared to α-tocopherol (IC50 > 0.6 mg/mL) and was comparable to the synthetic antioxidants butylated hydroxytoluene and butylated hydroxyanisole (IC50 ~ 0.35-0.34 mg/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-1IC50: anti-COX-2IC50 0.87) than synthetic anti-inflammatory drugs (0.02-0.44). No significant difference of in vivo 5-lipoxidase activity (IC50 0.95 mg/mL) than ibuprofen (IC50 0.93 mg/mL) indicated the potential anti-inflammatory properties of the title compound.