RESUMEN
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.
Asunto(s)
Alcaloides/farmacología , Antiinflamatorios no Esteroideos/farmacología , Inhibidores de la Ciclooxigenasa 2/farmacología , Gracilaria/química , Inhibidores de la Lipooxigenasa/farmacología , Morfolinas/farmacología , Alcaloides/química , Animales , Antiinflamatorios no Esteroideos/química , Antioxidantes/química , Antioxidantes/farmacología , Carragenina , Inhibidores de la Ciclooxigenasa 2/química , Edema/inducido químicamente , Edema/tratamiento farmacológico , Concentración 50 Inhibidora , Inhibidores de la Lipooxigenasa/química , Espectroscopía de Resonancia Magnética , Ratones Endogámicos BALB C , Morfolinas/química , Extractos Vegetales/química , Algas Marinas/química , Relación Estructura-ActividadRESUMEN
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).
Asunto(s)
Antioxidantes/aislamiento & purificación , Inhibidores de la Ciclooxigenasa/aislamiento & purificación , Gracilaria/química , Inhibidores de la Lipooxigenasa/aislamiento & purificación , Antiinflamatorios no Esteroideos/farmacología , Antioxidantes/química , Benzopiranos/química , Inhibidores de la Ciclooxigenasa/farmacología , Inhibidores de la Lipooxigenasa/farmacología , Opuntia , Oxígeno/química , Extractos Vegetales/química , Algas Marinas/químicaRESUMEN
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 â4)-4-O-sulphonato-(2-O-methyl)-ß-D-galactopyranosyl-(1â4)-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 â3)-4-O-sulphonato-(6-O-acetyl)-ß-D-galactopyranosyl-(1â4)-3,6-anhydro-(2-O-sulphonato)-α-D-galactopyranosyl-(1â3)-4-O-sulphonato-(6-O-acetyl)-ß-D-xylosyl-(1â3)-4-O-sulphonato-(6-O-acetyl)-ß-D-galactopyranosyl-(1â4)-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.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Antioxidantes/farmacología , Galactanos/farmacología , Algas Marinas/química , Inhibidores de la Enzima Convertidora de Angiotensina/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Galactanos/aislamiento & purificación , Rhodophyta/química , Relación Estructura-Actividad , SulfatosRESUMEN
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.