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Abstract Four previously undescribed antioxidative O -heterocyclic analogues, characterized as 3″-isopropyl-3c-{3b-[(2-oxo-3,4-dihydro-2 H -chromen-3-yl) methyl] butyl}-2″-butenyl-3′-hydroxy-2′-(2′b-methoxy-2′-oxoethyl)-3′, 4′-dihydro-2 H -pyran-4′-carboxylate (1), 2c-methylbutyl-6-[6c-(benzoyloxy)propyl]-6-methyl-tetrahydro-2 H -pyran-2-carboxylate (2), 6-{6b-[3′-(5′a-methyl propyl)-3′, 4′-dihydro-2 H -pyran-6′-yl] ethyl}-tetrahydro-2 H -pyran-2-one (3) and 7-(7c-methylpentyl)-hexahydro-2 H -chromen-2-one (4) were isolated from the ethylacetate:methanol fraction of the brown seaweed Sargassum wightii. Nuclear magnetic resonance and mass spectroscopic experiments unambiguously attributed their structural identities. Antihypertensive activities of the studied compounds were determined in terms of their angiotensin converting enzyme (ACE) inhibitory potential. The 2 H -pyranylcarboxylate derivative (1) displayed comparable activity (IC 50 0.08 mg/mL) with standard antihypertensive agent captopril (IC 50 0.07 mg/mL). The O -heterocyclic derivatives bearing 2 H -pyran-4′-carboxylate (1) and 2 H -pyran-2-carboxylate (2) frameworks showed significantly greater (p < 0.05) 1, 1-diphenyl-2-picryl-hydrazil radical quenching potential {IC 50 (1) 0.34 and IC 50 (2) 0.45 mg/mL} compared to the standard antioxidant α-tocopherol (IC 50 0.63 mg/mL). Structure-activity relationship analyses demonstrated that the electronic and lipophilic descriptors might significantly contribute towards the target bioactivities of 2 H -pyranylcarboxylates (1 and 2). Molecular docking simulations were carried out for ACE inhibition, and the binding energy obtained for the compounds (~7.04–8.48 kcal/mol) demonstrated their potential enzyme-ligand interactions. The potential of hitherto undescribed O -heterocyclic derivatives as natural antioxidant and antihypertensive functional food supplements and their utilization as therapeutic leads in the antihypertensive management were described in the present study. Graphical abstract Unlabelled Image Highlights • Four new O -heterocyclic analogues were isolated from seaweed Sargassum wightii. • 2 H -pyranylcarboxylates (1 – 2) display greater antioxidant activities than reference. • 2 H -pyran-4′-carboxylate (1) displayed an IC 50 of 0.08 mg/mL against ACE in vitro. • Electronic and lipophilic structural descriptors contributed towards bioactivities. • Molecular docking simulation showed ACE-ligand interactions in hypertension model. [ABSTRACT FROM AUTHOR]

Previously undescribed frido oleanene triterpenoids 2 α -hydroxy-(28,29)- frido -olean-12(13), 21(22)-dien-20-propyl-21-hex-4′( Z ) - enoate, 2 α -hydroxy-(28,29)- frido -olean-12(13), 21(22)-dien-20-prop-2( E )-en-21-butanoate and oxygenated labdane diterpenoids 2 α -hydroxy-8(17), (12 E ), 14-labdatriene, 3 β , 6 β , 13 α -tri hydroxy 8(17), 12 E , 14-labdatriene were purified from the ethyl acetate-methanol and dichloromethane fractions of the air-dried thalli of Sargassum wightii (Sargassaceae), a brown seaweed collected from the Gulf-of-Mannar of Penninsular India. Inhibitory potential of Δ 12 oleanenes towards protein tyrosine phosphatase-1B, the critical regulator of insulin-receptor activity were found to be significantly greater (IC 50 0.1 × 10 −2 and 0.09 × 10 −2 mg/mL, respectively) than the standard sodium metavanadate (IC 50 0.31 × 10 −2 mg/mL). Frido oleanene triterpenoids displayed greater antioxidant activities (IC 50DPPH 0.16–0.18 mg/mL) than the commercially available antioxidants, butylated hydroxytoluene and α-tocopherol (IC 50DPPH 0.25 and 0.63 mg/mL, respectively). In general, the oxygenated labdane diterpenoids displayed significantly lesser antioxidant and tyrosine phosphatase-1B inhibitory properties than those exhibited by the frido oleanenes. Bioactivities of the titled compounds were primarily determined by the electronic and lipophilic parameters and not by the steric descriptors. Molecular docking simulations and kinetic studies were employed to describe the tyrosine phosphatase-1B inhibitory mechanism. The previously undescribed frido oleanene triterpenoids might be used as potential anti-hyperglycaemic pharmacophore leads to reduce the risk of elevated postprandial glucose levels. [ABSTRACT FROM AUTHOR]

Previously undescribed aryl polyketide lactones, 4-(8-ethyl-tetrahydro-7-oxo-2 H -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) (IC 50 1,1-diphenyl-2-picrylhydrazyl radical scavenging 0.24–0.32 mg/mL) than α-tocopherol (IC 50 0.63 mg/mL). The title compounds displayed considerably greater 5-lipoxygenase inhibitory activity (IC 50 0.56 and 0.29 mg/mL, respectively) in conjunction with higher selectivity indices (anti-cycloxygense-1 IC50 /anti-cycloxygense-2 IC50 > 1) compared to non-steroidal anti-inflammatory drugs (SI aspirin 0.03, SI ibuprofen 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-2 H -pyranyl and oxa-cyclododecadienyl macrolactone featuring the aryl substituent from marine organisms with potential antioxidative and anti-inflammatory activities. [ABSTRACT FROM AUTHOR]

Antioxidant potential of three brown seaweeds,Anthophycus longifolius, Sargassum plagiophyllum, andSargassum myriocystum, obtained from the Gulf of Mannar region of India were evaluated utilizing differentin vitrosystems. Ethyl acetate (EtOAc) fraction ofAnthophycus longifoliusregistered significantly greater hydroxyl radical scavenging ability (IC500.19 mg/mL) and was effective in stabilizing the 2,2′-azino-bis-3-ethylbenzothiozoline-6-sulfonic acid (IC501.23 mg/mL) and 1,1-diphenyl-2-picryl-hydrazil (DPPH) radicals (IC500.48 mg/mL) (p< 0.05). No significant differences in hydrogen peroxide (H2O2) scavenging and ferrous ion chelating properties of the EtOAc extracts of the seaweeds were apparent. The utilities of the reverse-phase high-performance liquid chromatography (RP-HPLC) method hyphenated to diode-array detection for analyzing the fingerprints of phenolic constituents in the solvent extracts and fractions of the seaweeds were denoted. High-performance liquid chromatographic analysis indicated the presence of phenolic acids in the solvent extracts of seaweeds. This study demonstrated the potential use ofA. longifoliusas candidate species to be used as a nutritional food supplement/functional foods to increase the shelf life of food items for human consumption. [ABSTRACT FROM AUTHOR]