Minju Joy

O-heterocyclic derivatives with antibacterial properties from marine bacterium Bacillus subtilis associated with seaweed, Sargassum myriocystum

The brown seaweed, Sargassum myriocystum associated with heterotrophic bacterium, Bacillus subtilis MTCC 10407 (JF834075) exhibited broad-spectra of potent antibacterial activities against pathogenic bacteria Aeromonas hydrophila, Vibrio vulnificus, and Vibrio parahaemolyticus. B. subtilis MTCC 10407 was found to be positive for polyketide synthetase (pks) gene, and therefore, was considered to characterize secondary metabolites bearing polyketide backbone. Using bioassay-guided fractionation, two new antibacterial O-heterocyclic compounds belonging to pyranyl benzoate analogs of polyketide origin, with activity against pathogenic bacteria, have been isolated from the ethyl acetate extract of B. subtilis MTCC 10407. In the present study, the secondary metabolites of B. subtilis MTCC 10407 with potent antibacterial action against bacterial pathogens was recognized to represent the platform of pks-1 gene-encoded products. Two homologous compounds 3 (3-(methoxycarbonyl)-4-(5-(2-ethylbutyl)-5,6-dihydro-3-methyl-2H-pyran-2-yl)-butyl benzoate) and 4 [2-(8-butyl-3-ethyl-3,4,4a,5,6,8a-hexahydro-2H-chromen-6-yl)-ethyl benzoate] also have been isolated from the ethyl acetate extract of host seaweed S. myriocystum. The two compounds isolated from ethyl acetate extract of S. myriocystum with lesser antibacterial properties shared similar structures with the compounds purified from B. subtilis that suggested the ecological and metabolic relationship between these compounds in seaweed-bacterial relationship. Tetrahydropyran-2-one moiety of the tetrahydropyrano-[3,2b]-pyran-2(3H)-one system of 1 might be cleaved by the metabolic pool of seaweeds to afford methyl 3-(dihydro-3-methyl-2H-pyranyl)-propanoate moiety of 3, which was found to have no significant antibacterial activity. It is therefore imperative that the presence of dihydro-methyl-2H-pyran-2-yl propanoate system is essentially required to impart the greater activity. The direct involvement of polarisability (Pl) with the target bioactivity in 2 implied that inductive (field/polar) rather than the steric effect (parachor) appears to be the key factor influencing the induction of antibacterial activity. The present work may have a footprint on the use of novel O-heterocyclic polyketide products from seaweed-associated bacterium for biotechnological, food, and pharmaceutical applications mainly as novel antimicrobial secondary metabolites.

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

Abstract 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.

New sterols with anti-inflammatory potentials against cyclooxygenase-2 and 5-lipoxygenase from Paphia malabarica.

Abstract Marine bivalves occupy a leading share in the total edible molluscs at the coastline regions of south-eastern Asia, and are found to possess significant nutritional and biological potential. Various in vitro evaluation (antioxidant and anti-inflammatory) guided purification of ethyl acetate–methanol (EtOAc–MeOH) extract of bivalve clam, Paphia malabarica characterised two new sterol derivatives as 23-gem-dimethylcholesta-5-en-3β-ol (1) and (22E)-241,242-methyldihomocholest-5,22-dien-3β-ol (2) collected from the south-west coast of Arabian Sea. Their structures were unambiguously assigned on the basis of 1D, 2D NMR spectroscopy and mass spectrometry. The antioxidant and anti-inflammatory activities of 2 as determined by DPPH/ABTS+ radical scavenging and anti-cyclooxygenase-2/5-lipoxygenase assays were significantly greater (IC50 < 1 mg/mL) than 1 (IC50 > 1 mg/mL). Structure–activity relationship analysis revealed that the bioactivities of these compounds were directly proportional to the electronic and lipophilic parameters. This is the first report of the occurrence and characterisation of 23-gem-dimethyl-3β-hydroxy-Δ5-cholestane nucleus and C-30 dihomosterol from marine organisms.

Antibacterial polyketides from Bacillus amyloliquefaciens associated with edible red seaweed Laurenciae papillosa

Heterotrophic Bacillus amyloliquefaciens associated with edible red seaweed, Laurenciae papillosa was used to isolate antibacterial polyketide compounds. Antibacterial activity studies integrated with the outcome obtained by polyketide synthetase (pks) coding genes established that seaweed-affiliated bacterial flora had a wide-ranging antibacterial activities and potential natural product diversity, which proved that the bacterium is valuable reservoir of novel bioactive metabolites. Bioactivity-guided isolation of 3-(octahydro-9-isopropyl-2H-benzo[h]chromen-4-yl)-2-methylpropyl benzoate and methyl 8-(2-(benzoyloxy)-ethyl)-hexahydro-4-((E)-pent-2-enyl)-2H-chromene-6-carboxylate of polyketide origin, with activity against human opportunistic food pathogenic microbes, have been isolated from the ethyl acetate extract of B. amyloliquefaciens. Structure-activity relationship analysis revealed that hydrophobic descriptor of the polyketide compounds significantly contribute towards its antibacterial activity. Seaweed-associated microorganisms were shown to represent a potential source of antimicrobial compounds for food and health benefits. The antibacterial polyketide compounds described in the present study may find potential applications in the food industry to reduce food-borne pathogens.

Nutritional Composition of Edible Oysters (Crassostrea madrasensis L.)from the Southwest Coast of India

ABSTRACT Nutritional composition of edible oysters (Crassostrea madrasensis) from the wild and cultured growth habitats from the southwest coast of India were evaluated over 4 years (2008–2011) during the premonsoon season. The important nutritional qualities of this species have been correlated with chlorophyll-a concentration, sea surface temperature, and phytoplankton density in their growth environments. The higher proportions of total polyunsaturated fatty acids, eicosapentaenoic, and docosahexaenoic acids in the edible oysters collected from the wild habitats were significantly correlated with chlorophyll-a concentration revealing the role of the phytoplanktons to contribute to the occurrence of these vital fatty acids. The ideal atherogenic index (AI); thrombogenicity index (TI); hypocholesterolemic/hypercholesterolemic ratio (HH); and balanced quantities of vitamins, minerals, amino acids, and low cholesterol contents qualified C. madrasensis as a potential health food.

Nutritional Qualities of the Low-Value Bivalve Mollusks Paphia malabarica and Villorita cyprinoides at the Estuarine Waters of the Southwestern Coast of India

ABSTRACT The bivalve mollusks Paphia malabarica and Villorita cyprinoides collected from the estuarine system located in the southwest coastal waters of India were evaluated for their nutritional composition. A balanced essential to nonessential amino acid ratio (> 1.0) with a greater quantity of sulfur-containing amino acids in these species demonstrated that they could provide well-balanced protein depositions. The n-3/n-6 polyunsaturated fatty acid ratio in P. malabarica was found to be greater than 2, and, therefore, can be considered as a healthy diet. The C20–C22 long-chain polyunsaturated n-3 fatty acids (for example, docosahexaenoic acid and eicosapentaenoic acid) accounted for more than 23% of the total fatty acid content in P. malabarica as compared to about 7% in V. cyprinoides. P. malabarica showed greater hypocholesterolemic/hypercholesterolemic ratio (1.7) and lesser atherogenicity (0.7), thrombogenicity (0.3) indices when contrasted with those in V. cyprinoides, thereby indicating the nutritional superiority of the former. A greater content of vitamin D3 (> 150 IU), along with significant quantities of calcium and phosphorus (> 500 mg/100 g) in the clams, signified their importance in preventing osteoporosis. This study demonstrated the importance of bivalves, in particular, P. malabarica as a valued species for human consumption.

Previously undescribed antioxidative and anti-inflammatory chromenyls bearing 3H-isochromenone and furanyl-2H-chromenyl skeletons from the venerid clam, Paphia malabarica

Previously undescribed chromenyl derivatives, characterized as 7-(2′-ethyl-1′-hydroxynonan-2′-yl)-6,7,8,8a-tetrahydro-3H-isochromen-1-(5H)-one (1) and 61-(3-((E)-31b-(furan-2′-yl)-prop-31b-en-31-yl)-4a,5,6,8a-tetrahydro-8-methyl-2H-chromen-6-yl)-ethyl-5′′-methyl-hexanoate (2) were isolated from ethyl acetate-methanol extract of yellow-foot bivalve clam, Paphia malabarica. Their structures have skeletons composed of isochromen-(5H)-one and furanyl-2H-chromenyl moieties, which are reported for the first time in marine organism. These were characterized by extensive one and two-dimensional nuclear magnetic resonance, infrared, and high-resolution mass spectroscopic experiments. The title compounds were evaluated for therapeutic potentials with regard to anti-inflammatory and antioxidant properties compared to known standards. These compounds exhibited comparable 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS+) radical scavenging activities with α-tocopherol (IC50 ~0.6–0.7 mg/mL). The significantly higher anti-5-lipoxygenase activity of the title compounds (IC50 0.76–0.82 mg/mL) than ibuprofen (IC50 0.93 mg/mL) indicated their potential anti-inflammatory properties. The selectivity indices (IC50 anti-cyclooxygenase-1/IC50anti-cyclooxygenase-2) of compounds 1 (1.19) and 2 (1.31) well established its safety profiles as an anti-inflammatory when compared to known drug, ibuprofen (0.44). The target bioactivities of chromenyl derivatives were guided by hydrophobic and electronic parameters. These compounds can be used as potential bioactive leads in functional food and medicinal applications.

Previously undisclosed bioactive sterols from corbiculid bivalve clam Villorita cyprinoides with anti-inflammatory and antioxidant potentials

HIGHLIGHTSPreviously undisclosed specialized sterols were isolated from Villorita cyprinoides.Bioactive pluralities of compounds were dictated by hydrophobic factors.Molecular docking studies showed COX‐2 interactions in inflammation model.The titled compounds can be represented as new generation bio‐potential leads. ABSTRACT The estuarine Corbiculid bivalve black clam, Villorita cyprinoides collected from the Southwestern coastline regions of Arabian Sea are significant resources of nutritional and bioactive pluralities. The purification of ethyl acetate:methanol (EtOAc:MeOH) extract of V. cyprinoides characterized a previously undisclosed specialized abeo‐pregnane‐type sterol derivative 19 (10→5) abeo‐20‐methyl‐pregn‐10‐en‐3&bgr;‐yl‐hex‐(3′E)‐enoate (1) along with two cholestenols (22E),(241E)‐241,242‐dihomocholesta‐5,22,241‐trien‐3&bgr;‐ol (2) and (22E)‐241‐homocholesta‐5,22‐dien‐(3&bgr;,241&bgr;)‐diol (3). These compounds were characterized by comprehensive spectroscopic investigations. The anti‐inflammatory (anti‐cyclooxygenase‐1, 2/5‐lipoxidase) activities of 1 were considerably higher (IC50<1.10mg/mL) than 2–3 (IC50>1.10mg/mL). These studied compounds registered greater selectivity indices (˜1.03) against cyclooxygenase‐2 than cyclooxygenase‐1. The antioxidant property of abeo‐pregnane‐type sterol as determined by in vitro 2,2′‐azino‐bis‐(3‐ethyl‐benzthiazoline‐6‐sulfonic acid) quenching potential was significantly greater (IC50 0.94mg/mL) than those of substituted dihomocholesta‐trien‐ol (2) and homocholesta‐dien‐diol (3) (IC50>1.00mg/mL). Structure‐activity relationship studies demonstrated that bioactive potentials of the titled compounds were linearly related to their electronic factors along with optimum hydrophobic factors. In addition, molecular docking studies were performed in the active sites of COX‐2 and their binding energies and docking scores were well correlated with in vitro anti‐COX‐2 potentials.

Biogenic antioxidative and anti-inflammatory aryl polyketides from the venerid bivalve clam Paphia malabarica

Chemical investigation of ethyl acetate-methanol extract of the venerid bivalve clam Paphia malabarica led to isolation of three unprecedented aryl polyketide derivatives, characterized as (E)-12-(17-ethyl-tetrahydro-16-hydroxy-15-(methyl pentanoate)-14-oxo-2H-pyran-13-yl)-9-methyl-but-11-enyl benzoate (1), isobutyl-13-(6-(benzoyloxy)-10-methylpentyl)-tetrahydro-13-methyl-2H-pyran-17-carboxylate (2) and (13-(methoxycarbonyl)-11-((E)-18-ethylhexa-16,19-dienyl)-12-propyl-cyclohex-10-enyl)-methyl-3-hydroxy benzoate (3). The structures of the polyketides were assigned by extensive spectroscopic experiments. Compound 1 displayed comparatively greater 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical quenching potential (50% inhibitory concentration, IC50 ∼0.59mg/mL) than commercially available α-tocopherol (IC50 0.63mg/mL). Potential pro-inflammatory 5-lipoxygenase (5-LOX) inhibition potential (IC50 0.76-0.92mg/mL) of the polyketides in consonant with significantly greater anti-inflammatory selectivity indices (anti-cyclooxygense-1IC50/anti-cyclooxygense-2IC50>1) than non-steroidal anti-inflammatory agent ibuprofen (0.44) described the safety profile of the title compounds. Putative biosynthetic route by means of polyketide synthatase biocatalyzed pathways unambiguously established the structural assignments of the previously undescribed polyketide analogues. The potential of hitherto undescribed polyketides from P. malabarica as natural antioxidative and anti-inflammatory functional food ingredients was demonstrated in the present study.

Characterization and bioactive potentials of secondary metabolites from mollusks Crassostrea madrasensis and Amphioctopus marginatus

Abstract Chemical investigations of the ethyl acetate-methanol (EtOAc-MeOH) extract of the selected mollusks from the south-west coast of Arabian Sea led to the isolation of methyl-3-(26-phenylacetyloxy)-icosahydro-19-hydroxy-4,4,20-trimethylpicene-23-carboxylate (1) and methyl-3-(26-phenylacetyloxy)-icosahydro-1,19-dihydroxy-4,4,20-trimethylpicene-23-carboxylate (2) from Crassostrea madrasensis, whereas cholesta-5-en-3β-yl-(32-methyl-(30-((E)-34-amino-36-ethyl-39-oxohept-36-enyl)-pentanedioate (3) and 7-ethyl-9-vinyl-octahydroazuleno [1,8-bc]pyran-3,12-dione (4) were isolated from Amphioctopus marginatus. Their structures were assigned by detailed spectroscopic experiments. The studied compounds were checked for antioxidant and anti-inflammatory activities by various in vitro experiments. The radical quenching potential of 2,2-diphenyl-1-picrylhydrazyl and 2,2’-azino-bis-3-ethylbenzothiozoline-6-sulfonic acid diammonium salt were greater for 2 (IC50 0.85 and 1.10 mg/mL, respectively) than other studied compounds. The pro-inflammatory cyclooxygenase-2 inhibitory activity of 2 was greater (IC50 0.95 mg/mL) than those displayed by other studied compounds (>1.0 mg/mL). The 5-lipoxygenase inhibitory potential of 1 and 2 (~1.36 mg/mL) were greater than those displayed by 3 (1.64 mg/mL) and 4 (1.45 mg/mL).