Novel Furanyl-Substituted Isochromanyl Class of Anti-Inflammatory Turbinochromanone from Brown Seaweed Turbinaria conoides.

Organic extract of the brown seaweed Turbinaria conoides (Sargassaceae) was chromatographically fractionated to yield an undescribed furanyl-substituted isochromanyl metabolite, named as turbinochromanone, which was characterized as methyl 4-[(3S)-8-{[(3R)-4-ethyl-2,3-dihydrofuran-3-yl]methyl}-1-oxo-3,4-dihydro-1H-2-benzopyran-3-yl]butanoate. The isochromanyl derivative possessed comparable attenuation potential against 5-lipoxygenase (IC50 3.70 µM) with standard 5-lipoxygenase inhibitor drug zileuton (IC50 2.41 µM). Noticeably, the index of anti-inflammatory selectivity of turbinochromanone (∼1.7) was considerably greater than that exhibited by the standard agent diclofenac (1.06). Antioxidant properties of turbinochromanone against oxidants (IC50 ∼24 µM) further supported its potential anti-inflammatory property. Greater electronic properties (topological polar surface area of 61.8) along with comparatively lesser docking parameters of the studied compound with aminoacyl residues of targeted enzymes (cyclooxygenase-2 and 5-lipoxygenase) (binding energy of -11.05 and -9.40 kcal mol-1 , respectively) recognized its prospective anti-inflammatory potential. In an aim to develop seaweed-based natural anti-inflammatory leads, the present study isolated turbinochromanone as promising 5-lipoxygenase and cyclooxygenase-2 inhibitor, which could be used for pharmaceutical and biotechnological applications.

Anti-inflammatory ß-sitosterols from the Asiatic loop-root mangrove Rhizophora mucronata attenuate 5-lipoxygenase and cyclooxygenase-2 enzymes.

Four biogenic ß-sitosterol analogues were identified from methanolic extract of the leaves of loop-root mangrove Rhizophora mucronata. These were characterized as 4, 14, 23-trimethyl-3ß-sitosterol (1), 7-ethyl-3ß-sitosterol (2), sitosteryl-3ß-(33E)-pent-33-enoate (3) and 12α-hydroxy-3ß-sitosterol (4) based on comprehensive spectroscopic techniques. Anti-inflammatory activities of ß-sitosterol 4 against pro-inflammatory enzymes 5-lipoxygenase and cyclooxygenase-2 were found to be significantly higher (IC50 1.85 and 1.92 mM, respectively) compared to those demonstrated by compounds of 1-3 (p < 0.05). These ß-sitosterol analogues disclosed superior selectivity indices (1.43-2.07) with regard to inducible cyclooxygenase-2 than its constitutive isoform cyclooxygenase-1, when compared to the standard, ibuprofen (0.44). Antioxidant properties of 12α-hydroxy-ß-sitosterol (4) were found to be significantly greater (IC50 1.43-1.67 mM) than those of other sitosterol analogues. Structure-activity correlation analyses put forward that the bioactive potencies of the titled ß-sitosterols were positively correlated to their electronic parameters. Molecular docking simulations were carried out in the active sites of 5-lipoxygenase/cyclooxygenase-2, and the docking scores and binding energies of the studied ß-sitosterol analogues were positively correlated with their attenuation properties against 5-lipoxygenase and cyclooxygenase-2.

Marine macroalga-associated heterotroph Bacillus velezensis as prospective therapeutic agent.

Marine macroalgae and their accompanying microbial flora were proved to be the reservoir of potential bioactive compounds with promising pharmacological applications. Heterotrophic bacteria concomitant with the marine algae were isolated and screened for their antibacterial potential against clinically recognized pathogens. The bacterial isolate with greater bioactive properties was identified as Bacillus velezensis MBTDLP1 (phylum Firmicutes), which was isolated from the marine macroalga Laurencia papillosa, by integrated morphological, biochemical and molecular characterization. B. velezensis showed promising antibacterial property against methicillin-resistant Staphylococcus aureus and Vibrio parahemolyticus with inhibition zone of 32-36 mm. Organic ethyl acetate extract of the isolate also displayed prospective antibacterial activity against the test pathogens (minimum inhibitory concentration 7.5-15 µg/mL), coupled with promising antioxidant (IC50 0.1-0.9 mg/mL against oxidants), anti-inflammatory (IC50 0.01 mg/mL against 5-lipoxygenase), and carbolytic enzyme attenuation properties (IC50 0.1-0.4 mg/mL in response to α-amylase and α-glucosidase). Significant anticancer potential against breast carcinoma (MCF-7) cells (IC50 0.03 mg/mL) coupled with lesser cytotoxicity to the normal fibroblast (3T3L) cells (IC50 0.14 mg/mL) were also recognized. The apoptosis assay could give reasonable outcome as the organic extract of B. velezensis induced apoptosis to 81% of the cancer cells while maintaining almost 60% viability in normal cells. The results put forward that B. velezensis MBTDLP1 could be used to isolate bioactive compounds with therapeutic potential and biomedical applications.

First report of antioxidant 1H-benzochromenone from muricid gastropod Chicoreus ramosus as dual inhibitors of pro-inflammatory 5-lipoxygenase and carbolytic enzymes.

Chromene derivatives with manifold structural framework and pharmacological properties were ubiquitous in the mollusks of marine origin. A previously undescribed 1H-benzochromenone was isolated through bioassay-guided chromatographic purification of the organic extract of the marine gastropod mollusk Chicoreus ramosus. The compound was characterised as 6-(2',2'-dimethyl)-3'-en-1'-yl-1'-oxy)-3-hydroxy-1H-benzo[c]chromene-2(10aH)-one based on integrated spectroscopic analysis. The antioxidant studies by employing the stable free radicals reported that the antioxidant activity (IC50 1.4-1.6 mM) was comparable to α-tocopherol (IC50 1.4-1.7 mM). The attenuating potential of the studied compound against pro-inflammatory 5-lipoxygenase (IC50 2.12 mM) was significantly greater than that exhibited by anti-inflammatory drug ibuprofen (IC50 4.4 mM), whereas its inhibitory properties against carbolytic α-amylase (IC50 ∼0.72 mM) was comparable with that displayed by acarbose (IC50 0.43 mM). The present study recognised the potential of 1H-benzochromenone derivative isolated from C. ramosus as important pharmaceutical lead with anti-diabetic and anti-inflammatory potentials to reduce the risk of hyperglycaemia and inflammatory pathologies.

Antioxidative dolabellanes and dolastanes from brown seaweed Padina tetrastromatica as dual inhibitors of starch digestive enzymes.

New dolabellanes {6-methoxy-dolabella-8(17),12-diene-10ß,18-diol (1), 3-methoxy-dolabella-12(18)-ene-4ß-ol (2), 3-methoxy-dolabella-10,18(19)-diene-5α,8ß-diol (3)} and dolastanes {2,7-dimethoxy-14α-hydroxy-dolasta-1(15),9-diene (4) and 4,7-dimethoxy-9ß,14α-dihydroxy-dolasta-1-ene (5)} were identified from brown seaweed Padina tetrastromatica (family Dictyotaceae), collected from the southeast coast of India. Compounds 1-3 were found to possess dolabellane skeleton with [9.3.0] cyclotetradecane framework whereas, 4-5 were composed of tricyclic diterpenes with linear arrangement of six-seven-five fused alicyclic rings. Compounds 3 and 5 registered greater antioxidative activities (IC50 ≤0.63 mg/mL) than other analogues (IC50 ≥0.65 mg/mL), whereas their attenuating potentials against carbolytics α-amylase and α-glucosidase (IC50 ∼0.12-0.14 mg/mL) were comparable with those displayed by acarbose (IC50 0.14-0.12 mg/mL). Bioactive potentials of titled compounds were assessed by electronic and lipophilic parameters. The lesser binding energies of 3 (-9.71 kcal/mol) and 5 (-8.59 kcal/mol) through molecular docking demonstrated their effective hydrogen bonding interactions with α-amylase. Thus, dolabellanes and dolastanes might be used as anti-diabetic and antioxidant leads to reduce the risk of hyperglycaemia.

Marine Algae as a Potential Source for Anti-diabetic Compounds - A Brief Review.

BACKGROUND: Diabetes Mellitus (DM) is a major chronic metabolic disorder characterized by hyperglycemia that leads to several complications such as retinopathy, atherosclerosis, nephropathy, etc. In 2019, it was estimated that about 463 million people had diabetes, and it may increase up to 700 million in 2045. Marine macroalgae are the rich source of bioactive compounds for the treatment of diabetes mellitus. OBJECTIVE: This review summarizes the recent epidemiology and possible use of marine macroalgae-derived bioactive compounds for the protection against chronic metabolic disease, diabetes mellitus and marine macroalgae as a nutraceutical supplement. CONCLUSION: The present therapies available for diabetes treatment are oral medicines and insulin injections. But continuous use of synthetic medicines provides low therapeutic with many side effects. In continuing search of anti-diabetic drugs, marine macroalgae remain as a promising source with potent bioactivity. Among existing marine algae, red and brown algae are reported to show anti-diabetic activity. Hence, the present review focuses on the epidemiology, diabetes biomarkers and different secondary bioactive compounds present in marine macroalgae to treat diabetes mellitus.

Moving away from traditional antibiotic treatment: can macrocyclic lactones from marine macroalga-associated heterotroph be the alternatives?

Intertidal red algae Hypnea valentiae associated Bacillus amyloliquefaciens MTCC 12716 revealed potential inhibitory effects on the growth of drug-resistant pathogens. In the genome of B. amyloliquefaciens MTCC 12716, biosynthetic gene clusters encoding antibacterial metabolites were predicted, which might be expressed and contributed to the broad-spectrum anti-infective activity. Three homologue members of the 24-membered macrocyclic lactone family, named as bacvalactones 1-3 bearing 13-O-ethyl (1); 15-O-furanyl-13-O-isobutyl-7-O-propyl-propanoate (2); and 15-O-furanyl-13-O-isobutyl-7-O-propyl-propanoate-7,24-dimethyl (3) functionalities, were acquired through bioactivity-guided purification. The macrocyclic lactones displayed bactericidal activity against opportunistic pathogens causing nosocomial infections, for instance, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecalis (VREfs), and multidrug-resistant strains of Pseudomonas aeruginosa and Klebsiella pneumonia with MIC ≤ 3.0 µg/mL, whereas standard antibiotics ampicillin and chloramphenicol were active only at concentrations of ≥ 6.25 mg/mL. The biosynthetic pathway of macrocyclic lactones that are generated by trans-AT polyketide synthases through stepwise extension of an acetyl starter unit by eleven sequential Claisen condensations with malonyl-CoA was established, and the structures were correlated with the gene organization of the mln operon, which encompasses nine genes mln A-I (approximately 47 kb in size). The best binding poses for each compounds (1-3) with Staphylococcus aureus peptide deformylase (SaPDF) unveiled docking scores (≥ 9.70 kcal/mol) greater than that of natural peptide deformylase inhibitors, macrolactin N and actinonin (9.14 and 6.96 kcal/mol, respectively), which supported their potential in vitro bioactivities. Thus, the present work demonstrated the potential of macrocyclic lactone for biotechnological and pharmaceutical applications against emerging multidrug-resistant pathogens. Key Points •Three antibacterial bacvalactones were identified from the symbiotic bacterium. •The symbiotic bacterial genome was explored to identify the biosynthetic gene clusters. •Trans-AT pks-assisted mln biosynthetic pathway of the macrocyclic lactone was proposed. •In silicomolecular interactions of the bacvalactones with S. aureus PDF were analyzed.

First report of antioxidant abeo-labdane type diterpenoid from intertidal red seaweed Gracilaria salicornia with 5-lipoxygenase inhibitory potential.

Phytochemical investigation on the biologically active compounds of seaweed Gracilaria salicornia {(C. Agardh) E.Y. Dawson} (family Gracilariaceae) guided to the separation of a previously unreported abeo-labdane class of diterpenoid. The compound was characterized as methyl-16(13→14)-abeo-7-labdene-(12-oxo) carboxylate by extensive spectroscopic experiments, and comparison with the related compounds. The studied compound registered significantly greater activities against pro-inflammatory 5-lipoxygenase (IC50 0.86 mg/mL) than that exhibited by non-steroidal anti-inflammatory agent ibuprofen (IC50 0.92 mg/mL, P < 0.05). Likewise, this compound exhibited comparable radical quenching (1, 1-diphenyl-2-picryl-hydrazil) activity (IC50 0.66 mg/mL) as standard antioxidant agent α-tocopherol (IC50 0.62 mg/mL).

First report of substituted 2H-pyranoids from brown seaweed Turbinaria conoides with antioxidant and anti-inflammatory activities.

The organic extract of Turbinaria conoides, a brown seaweed harvested from the Gulf of Manner region of Indian peninsular was chromatographically fractionated to yield three substituted 2H-pyranoids, namely methyl-21-yl-[5', 6'- dihydro-5'-yl-{54-(4-hydroxybenzoyl)-oxy-(52-methylbutyl)}-3'-methyl-2H-pyran]-21-methyl butanoate (1), 11-[(3', 6'-dihydro-4'-methyl-2'-oxo-2H-pyran-3'-yl)methyl]-10-methylhexyl benzoate (2), and [6-ethyl-3,4-dimethyl-(tetrahydro-2', 2', 6'-trimethyl-2H-pyran-3'-yl)-2,5-cycloheptadiene]-1-propanoate (3). The compounds 1 and 2 bearing 2H-pyranyl-4-hydroxybenzoyl and 2H-pyranyl-10-methylhexylbenzoate moieties exhibited potential antioxidant activities (IC50 0.54-0.69 mg mL-1) as commercial antioxidant (α-tocopherol IC50 0.63-0.73 mg mL-1). Likewise, potential bioactivity of the 2H-pyran derivative, 1 against 5-lipoxygenase (IC50 ∼ 1 mg mL-1) along with higher index of selectivity (COX-1 inhibitoryIC50/COX-2 inhibitoryIC50 1.88) indicated their selective anti-inflammatory properties against inducible inflammatory mediators than that displayed by commercially available non-steroidal anti-inflammatory drug (ibuprofen, 0.44). Structure activity relationship analysis of the studied compounds showed that the antioxidative and anti-inflammatory properties were directly proportional to their electronic properties. The previously undescribed 2H-pyranoids might constitute as potential antioxidative and anti-inflammatory pharmacophores for medicinal applications. [Formula: see text].

First report of antioxidative 2H-chromenyl derivatives from the intertidal red seaweed Gracilaria salicornia as potential anti-inflammatory agents.

Phytochemical investigation on biologically active compounds of an intertidal red seaweed Gracilaria salicornia (family Gracilariaceae) guided to the separation of two previously undisclosed 2H-chromenyl derivatives. The compounds were characterised as 4'-[10'-[7-hydroxy-2,8-dimethyl-6-(pentyloxy)-2H-chromen-2-yl]ethyl]-3',4'-dimethyl-cyclohexanone (1) and 3'-[10'-(8-hydroxy-5-methoxy-2,6,7-trimethyl-2H-chromen-2-yl)ethyl]-3'-methyl-2'-methylene cyclohexyl butyrate (2) by extensive spectroscopic experiments. The studied metabolites recorded prospective bioactivities against 5-lipoxygenase (IC50 < 2.50 mM), whereas their selectivity indices were significantly greater (∼1) than ibuprofen (0.89) (p < 0.05), which attributed higher anti-inflammatory selectivity of 2H-chromenyl compounds against inducible cyclooxygenase-2 than its constitutive pro-inflammatory isoform of cyclooxygenase-1. The radical scavenging potential of 2 against oxidants, 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis-3 ethylbenzothiozoline-6-sulfonic acid were higher (IC50 < 1.35 mM) than standard antioxidant, α-tocopherol (IC50 1.42-1.79 mM). The greater hydrogen bond interactions and binding affinity of 2 (-7.35 kcal mol-1) bearing 2H-chromenyl ethyl-3'-methyl-4'-methylenecyclohexyl butyrate moiety with 5-lipoxygenase, along with higher electronic properties and permissible hydrophobic-hydrophilic balance, manifested towards its greater anti-inflammatory activity than 1.

Previously undescribed benzoxepins with bioactivities against inducible pro-inflammatory cyclooxygenase and lipoxygenase from Rhizophora annamalayana Kathir.

Two unprecedented benzoxepins were obtained from the ethyl acetate fraction of the leaves of Rhizophora annamalayana Kathir, and characterized as 4-(11-(hydroxymethyl)-10-methylpentan-2-yl)-4, 5-dihydrobenzo[c]oxepin-1(3H)-one (1) and (E)-methyl-14-hydroxy-4-(11-(5-hydroxy-1-oxo-3,4,5-tetrahydrobenzo[c]oxepin-4-yl)ethyl)-10-methylhept-11-enoate (2). The benzoxepin 2 exhibited greater 1, 1-diphenyl-2-picrylhydrazyl and 2, 2'-azino-bis-3 ethylbenzothiozoline-6-sulfonic acid diammonium radical scavenging assays (IC50 0.68 and 0.84 mg/mL, respectively) than those recorded with 1 (IC50 0.70 and 0.89 mg/mL, respectively). The tetrahydrobenzo[c]oxepin analogue (2) exhibited significantly great cyclooxygenase-2 and 5-lipoxygenase inhibitory properties (IC50 0.87 and 0.94 mg/mL, respectively), while compared with its dihydrobenzo[c]oxepin-1(3H)-one isoform (1) (IC50 1.16 and 1.64 mg/mL, respectively). The dihydrobenzo[c]oxepin-1(3H)-one isoform (2) exhibited significantly greater selectivity index (~2) than synthetic ibuprofen (0.44) (p < 0.05), which attributed the higher anti-inflammatory selectivity of the former against inducible pro-inflammatory cyclooxygenase-2 than its constitutive isoform (cyclooxygenase-1). No significant difference in 5-lipoxygenase (5-LOX) inhibitory activities were apparent between compound 2 (IC50 0.94 mg/mL) and synthetic ibuprofen (IC50 0.93 mg/mL).

Previously undescribed antioxidative O-heterocyclic angiotensin converting enzyme inhibitors from the intertidal seaweed Sargassum wightii as potential antihypertensives.

Four previously undescribed antioxidative O-heterocyclic analogues, characterized as 3″-isopropyl-3c-{3b-[(2-oxo-3,4-dihydro-2H-chromen-3-yl) methyl] butyl}-2″-butenyl-3'-hydroxy-2'-(2'b-methoxy-2'-oxoethyl)-3', 4'-dihydro-2H-pyran-4'-carboxylate (1), 2c-methylbutyl-6-[6c-(benzoyloxy)propyl]-6-methyl-tetrahydro-2H-pyran-2-carboxylate (2), 6-{6b-[3'-(5'a-methyl propyl)-3', 4'-dihydro-2H-pyran-6'-yl] ethyl}-tetrahydro-2H-pyran-2-one (3) and 7-(7c-methylpentyl)-hexahydro-2H-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 2H-pyranylcarboxylate derivative (1) displayed comparable activity (IC50 0.08 mg/mL) with standard antihypertensive agent captopril (IC50 0.07 mg/mL). The O-heterocyclic derivatives bearing 2H-pyran-4'-carboxylate (1) and 2H-pyran-2-carboxylate (2) frameworks showed significantly greater (p < 0.05) 1, 1-diphenyl-2-picryl-hydrazil radical quenching potential {IC50 (1) 0.34 and IC50 (2) 0.45 mg/mL} compared to the standard antioxidant α-tocopherol (IC50 0.63 mg/mL). Structure-activity relationship analyses demonstrated that the electronic and lipophilic descriptors might significantly contribute towards the target bioactivities of 2H-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.

Antioxidative and anti-inflammatory pyranoids and isochromenyl analogues from Corbiculid bivalve clam, Villorita cyprinoides.

Bivalve black clam, Villorita cyprinoides is traditional seafood in Southwestern coast of Arabian Sea. In this study, bioactivity-guided purification of ethyl acetate:methanol extract of black clam was carried out. Two irregular meroterpenoids {tetrahydro-3-methoxy-5-((E)-8,12-dimethyloct-8-enyl)-pyran-2-one (1) and dihydro-5-(8-(9,12-dihydro-8-methyl-11-propyl-2H-pyran-8-yl)-ethyl)-furan-2(3H)-one (2)} and two hexahydro-isochromenyl-meroterpenoids (3-4) were identified. The structures were characterized by detailed spectroscopy and their antioxidant/anti-inflammatory potentials were evaluated. Compound 2 registered significantly greater 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ability (IC50 <0.65 mg/mL) than other analogues (IC50 ≥0.70 mg/mL). Ferrous ion (Fe2+) chelating ability was higher for 1-2 (IC50 ∼0.84 mg/mL) than α-tocopherol (IC50 0.89 mg/mL). The 5-lipoxygenase inhibitory potential of furano-meroterpenoid analogue, 2 (IC50 0.76 mg/mL) was greater than other compounds (IC50 >0.90 mg/mL). An optimum hydrophobic-hydrophilic balance of furano-meroterpenoid and lesser steric bulk manifested towards its greater bioactivities compared to other compounds. These anti-inflammatory and antioxidant leads could be used as potential functional food components.

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.

In vitro bioactive analysis and antioxidant activity of two species of seaweeds from the Gulf of Mannar.

Evaluation of in vitro standard antioxidant assays, such as 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis-3 ethylbenzothiozoline-6-sulphonic acid diammonium salt (ABTS+) radical scavenging, lipid peroxidation inhibitory (or thiobarbituric acid formation inhibitory activity) and ferrous ion (Fe+2) chelating activities of different solvent extracts of seaweeds, Jania rubens and Kappaphycus alvarezii collected from the Gulf of Mannar of the Peninsular India, were carried out. The methodology utilised bioactivity-guided extraction of seaweed with effective solvent comprised classical chromatographic and spectroscopic techniques. The ethyl acetate extraction of seaweeds displayed significantly greater antioxidant activity than dichloromethane and n-hexane extraction. Bioactivity-guided chromatographic separation of the ethyl acetate extract of seaweeds with potentially greater antioxidant activities, yielded 6α-methoxy-4bß-methyl-7ß-vinyl-1,2,3,4,4a,4b,5,6,7,8,8a,9-dodecahydro-2ß-phenanthrenol (1) from J. rubens, whereas K. alvarezii yielded 2ß-ethyl-9-oxo-5α-vinyl-1,2,5,5a,6,7,8,9-octahydroheptalene-10,1-carbolactone (2) and methyl-2-ethyl-9-oxo-5α-vinyl-1,2,5,5a,6,7,10,10a-octahydroheptalene-1α-carboxylate (3). Compound 1 displayed significantly greater DPPH scavenging activities (IC50 0.22 mg/mL) than α-tocopherol (IC50 0.63 mg/mL). The order of DPPH radical-scavenging activities were compounds 1 > 2 > 3.

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).

Biogenic guaianolide-type sesquiterpene lactones with antioxidative and anti-inflammatory properties from natural mangrove hybrid Rhizophora annamalayana.

Previously undescribed guaianolide-type sesquiterpene lactones were isolated from the chloroform fraction of the natural hybrid mangrove Rhizophora annamalayana, and were characterised as (Z)-3α,4,5,6-tetrahydro-5α-isobutyl-2ß-(methoxymethyl)-7-methyl-3H-cyclohepta[b]carbolactone (1) and (7Z)-isopentyl 3α,4,5,6,7,8-hexahydro-2ß-((E)-11-methylbut-10-enyl)-1-oxo-2H-cyclohepta[b]furan-6-carboxylate (2). Compound 2 displayed greater antioxidative activities {1, 1-diphenyl-2-picrylhydrazyl (DPPH) and 2, 2'-azino-bis-3 ethylbenzothiozoline-6-sulphonic acid diammonium salt (ABTS), IC50 0.65 and 0.62 mg/mL, respectively)} compared to 1 (IC50 0.83 and 1.14 mg/mL, respectively) (p < 0.05). Compound 2 recorded no significant difference in DPPH. scavenging activities (IC50 0.65 mg/mL) compared to α-tocopherol (IC50 0.63 mg/mL). Pro-inflammatory 5-lipoxygenase inhibitory activity of 2 was found to be comparable (IC50 0.98 mg/mL) to that displayed by synthetic anti-inflammatory drug ibuprofen (IC50 0.93 mg/mL). Compound 2 showed significantly greater selectivity index (anti-cyclooxygenase-1/anti-cyclooxygenase-2 = 2.15) than non-steroidal anti-inflammatory ibuprofen (<0.5) (p < 0.05), and therefore, might be used as selective cyclooxygenase-2 inhibitor. The hitherto undescribed guaianolide lactones might be used as potential anti-inflammatory and antioxidative pharmacophore leads.

First report of two new antioxidative meroterpeno 2H-pyranoids from short-necked yellow-foot clam Paphia malabarica (family: Veneridae) with bioactivity against pro-inflammatory cyclooxygenases and lipoxygenase.

Two new meroterpeno 2H-pyranoids were isolated from the EtOAc:MeOH extract of yellow-foot clam Paphia malabarica. The structures of these newly reported compounds were elucidated based on spectroscopic interpretations. This is the first report of biogenic 2H-pyrans bearing decadienyl and allyloxy-(isopentanyl)-cyclohexene skeletons from marine biota. The extended C18 sesquiterpenoid with prenylated irregular farnesene framework was characterised as 2-((E)-deca-1,8-dien-10-yl)-11,12-dihydro-13-propyl-2H-pyran (1). The compound 2, 1'-((10E)-10-(10-(pentan-4-yl)-cyclohex-4-enyl)-allyloxy)-tetrahydro-2',2'-dimethyl-2H-pyran represents the first example of naturally occurring C21 prenylated bisabolene-type meroterpenoid, whereas tetrahydro-2',2'-dimethyl-2H-pyran remains attached at C-2' position of rearranged bisabolene framework formed by allyloxy linkage. The antioxidant activities (DPPH/ABTS+) of 1 and 2 were comparable (IC50 < 1.0 mg/mL) with α-tocopherol. In addition, these compounds exhibited greater activity against cyclooxygenase-2 than COX-1, and the selectivity indices were significantly lesser (~1.1). No significant differences in anti-5-lipoxygenase activity of 1 and 2 (IC50 1.02-1.06 mg/mL) than ibuprofen (IC50 0.93 mg/mL) indicated the potential anti-inflammatory properties of title compounds.

Two rare antioxidative prenylated terpenoids from loop-root Asiatic mangrove Rhizophora mucronata (Family Rhizophoraceae) and their activity against pro-inflammatory cyclooxygenases and lipoxidase.

Two new biogenic prenylated terpenoids were isolated from the methanol extract of Rhizophora mucronata. The extended C20 sesquiterpenoid with prenylated guaiane framework was characterised as (4E, 8Z)-3, 3a, 6, 7-tetrahydro-3, 9-dimethyl-5-(6-methylheptan-2-yl) cycloocta[b]furan-2-(9aH)-one (1). (35E)-1,2,3,5,6,6-icosahydro-4,4,8b,10,14,17,20,20-octamethylpicen-3-yl-34,35-dimethyloct-31-enoate (2) represents the first example of naturally occurring C40 prenylated oleanane-type triterpenoid, whereas one 4,5-dimethyloct-5-enoate side chain remains attached at C-3 position of the oleanane framework formed by the E-ring closure of C30 saccharide moiety. The structures of the compounds were elucidated using NMR and mass spectrometric analysis. Compound 1 was found to have significantly greater antioxidant activities (IC50 ~ 0.75 mg/mL) compared to 2 (IC50 > 0.80 mg/mL). No significant differences in anti-cyclooxygenase-2 of these compounds were discernable (IC50 0.8 - 0.9 mg/mL), whilst compound 1 showed greater anti-5-lipoxidase activities (IC50 ~ 0.8 mg/mL) those that of 2 (IC50 0.96 mg/mL). Bioactivities of the prenylated terpenoids were inversely proportional to lipophilic and bulk descriptors.

Characterization of substituted aryl meroterpenoids from red seaweed Hypnea musciformis as potential antioxidants.

The ethyl acetate fraction of red seaweed Hypnea musciformis was purified to yield three substituted aryl meroterpenoids, namely, 2-(tetrahydro-5-(4-hydroxyphenyl)-4-pentylfuran-3-yl)-ethyl-4-hydroxybenzoate (1), 2-2-[(4-hydroxybenzoyl)-oxy]-ethyl-4-methoxy-4-2-[(4-methylpentyl)oxy]-3,4-dihydro-2H-6-pyranylbutanoic acid (2) and 3-((5-butyl-3-methyl-5,6-dihydro-2H-pyran-2-yl)-methyl)-4-methoxy-4-oxobutyl benzoate (3). The structures of these compounds, as well as their relative stereochemistries, were confirmed by exhaustive NMR spectroscopic data analyses. Compound 1 exhibited similar 2,2'-diphenylpicrylhydrazyl radical inhibiting and Fe(2+) ion chelating activities (IC50 25.05 and 350.7µM, respectively) as that of commercial antioxidant gallic acid (IC50 32.3 and 646.6µM, respectively), followed by 3 (IC50 231.2 and 667.9µM, respectively), and 2 (IC50 322.4 and 5115.3µM, respectively), in descending order of activities. Structure-activity relationship analysis revealed that the antioxidant activities of these compounds were directly proportional to the steric and hydrophobic parameters. The seaweed derived aryl meroterpenoids might serve as potential lead antioxidative molecules for use in pharmaceutical and food industries.