Lipopeptide Epimers and a Phthalide Glycerol Ether with AChE Inhibitory Activities from the Marine-Derived Fungus Cochliobolus Lunatus SCSIO41401.

A pair of novel lipopeptide epimers, sinulariapeptides A (1) and B (2), and a new phthalide glycerol ether (3) were isolated from the marine algal-associated fungus Cochliobolus lunatus SCSIO41401, together with three known chromanone derivates (4-6). The structures of the new compounds, including the absolute configurations, were determined by comprehensive spectroscopic methods, experimental and calculated electronic circular dichroism (ECD), and Mo2 (OAc)4-induced ECD methods. The new compounds 1-3 showed moderate inhibitory activity against acetylcholinesterase (AChE), with IC50 values of 1.3-2.5 µM, and an in silico molecular docking study was also performed.

Leucanone A and naamine J, glycerol ether lipid and imidazole alkaloid from the marine sponge Leucandra sp.

Chemical investigation on CH2Cl2 extract of the marine sponge Leucandra sp. afforded two new compounds named leucanone A (1) and naamine J (2), together with eight known compounds (3-10). Their structures were elucidated on the basis of NMR spectroscopic analyses, and comparing with the literature. The cytotoxic activities of the compounds were evaluated against four cancer cell lines, and compound 2 showed mild cytotoxic activities against MCF-7, A549, HeLa, and PC9 cancer cell lines with IC50 values in the range of 20.1-45.3 µM.

Synthetic archaeosome vaccines containing triglycosylarchaeols can provide additive and long-lasting immune responses that are enhanced by archaetidylserine.

The relation between archaeal lipid structures and their activity as adjuvants may be defined and explored by synthesizing novel head groups covalently linked to archaeol (2,3-diphytanyl-sn-glycerol). Saturated archaeol, that is suitably stable as a precursor for chemical synthesis, was obtained in high yield from Halobacterium salinarum. Archaeosomes consisting of the various combinations of synthesized lipids, with antigen entrapped, were used to immunize mice and subsequently determine CD8(+) and CD4(+)-T cell immune responses. Addition of 45 mol% of the glycolipids gentiotriosylarchaeol, mannotriosylarchaeol or maltotriosylarchaeol to an archaetidylglycerophosphate-O-methyl archaeosome, significantly enhanced the CD8(+) T cell response to antigen, but diminished the antibody titres in peripheral blood. Archaeosomes consisting of all three triglycosyl archaeols combined with archaetidylglycerophosphate-O-methyl (15/15/15/55 mol%) resulted in approximately additive CD8(+) T cell responses and also an antibody response not significantly different from the archaetidylglycerophosphate-O-methyl alone. Synthetic archaetidylserine played a role to further enhance the CD8(+) T cell response where the optimum content was 20-30 mol%. Vaccines giving best protection against solid tumor growth corresponded to the archaeosome adjuvant composition that gave highest immune activity in immunized mice.

Core and intact polar glycerol dibiphytanyl glycerol tetraether lipids of ammonia-oxidizing archaea enriched from marine and estuarine sediments.

Glycerol dibiphytanyl glycerol tetraether (GDGT)-based intact membrane lipids are increasingly being used as complements to conventional molecular methods in ecological studies of ammonia-oxidizing archaea (AOA) in the marine environment. However, the few studies that have been done on the detailed lipid structures synthesized by AOA in (enrichment) culture are based on species enriched from nonmarine environments, i.e., a hot spring, an aquarium filter, and a sponge. Here we have analyzed core and intact polar lipid (IPL)-GDGTs synthesized by three newly available AOA enriched directly from marine sediments taken from the San Francisco Bay estuary ("Candidatus Nitrosoarchaeum limnia"), and coastal marine sediments from Svalbard, Norway, and South Korea. Like previously screened AOA, the sedimentary AOA all synthesize crenarchaeol (a GDGT containing a cyclohexane moiety and four cyclopentane moieties) as a major core GDGT, thereby supporting the hypothesis that crenarchaeol is a biomarker lipid for AOA. The IPL headgroups synthesized by sedimentary AOA comprised mainly monohexose, dihexose, phosphohexose, and hexose-phosphohexose moieties. The hexose-phosphohexose headgroup bound to crenarchaeol was common to all enrichments and, in fact, the only IPL common to every AOA enrichment analyzed to date. This apparent specificity, in combination with its inferred lability, suggests that it may be the most suitable biomarker lipid to trace living AOA. GDGTs bound to headgroups with a mass of 180 Da of unknown structure appear to be specific to the marine group I.1a AOA: they were synthesized by all three sedimentary AOA and "Candidatus Nitrosopumilus maritimus"; however, they were absent in the group I.1b AOA "Candidatus Nitrososphaera gargensis."

Ceratodictyols, 1-glyceryl ethers from the red alga-sponge association Ceratodictyon spongiosum/Haliclona cymaeformis.

Six 1-glyceryl ethers (1-6) were isolated from the red alga-sponge assemblage Ceratodictyon spongiosum/Haliclona cymaeformis. Structural assignments were conducted by interpretation of spectroscopic data and the modified Mosher's method. Four allylic alcohols were obtained as a pair of epimeric mixtures (3/4 and 5/6). These glyceryl ethers exhibited weak cytotoxic activity against HeLa human cervical cancer cells.

[Effect of 1-O-alkyl-glyceride ethers isolated from lipids of the squid Berrytteuthis magister liver on lipid metabolism and hematological parameters of rats with experimental dislipidemia].

On the white Wistar rats with alimentary dyslipidemia investigated influence 1-O-alkyl-glycerides ethers (AGE), received by a method of hydrolysis 1-O-alkyl-diacylglycerides from lipids of the squid Berryteuthis magister liver, on a lipid metabolism, hepatobiliary functions of liver, antioxidant systems and parameters of blood. Are revealed antioxidant, antianemia and immunoactive properties of AGE. AGE raise a level of glucose and activity of enzymes hepatobiliary systems in blood, interfere the decrease of a cholesterol in blood.

1-O-alkylglycerols from the hepatopancreas of the crab Paralithodes camtschaticus, liver of the squid Berryteuthis magister, and liver of the skate Bathyraja parmifera, and their anticancer activity on human melanoma cells.

1-O-alkylglycerols (AKG) are a class of natural ether lipids derived from 1-O-alkyl-2,3-diacyl-sn-glycerols by deacylation. In this study, 1-O-alkylglycerol (AKG) composition was investigated in the hepatopancreas lipids of the crab Paralithodes camtschaticus and the liver lipids of the squid Berryteuthis magister and the skate  Bathyraja parmifera. One of the principal AKG in marine organisms was 1-O-hexadecyl-sn-glycerol (AKG 16:0). To assess AKG influence on melanoma, we evaluated the cytotoxicity and antiproliferative actions of natural AKG 16:0 and synthetic 1-O-octyl-sn-glycerol (AKG 8:0) on three human melanoma cell lines SK-Mel-5, SK-Mel-28, and RPMI-7951. Natural AKG 16:0 in concentration up to 20 µM was not toxic to all cell lines. AKG 8:0 showed no toxicity to cells SK-Mel-5 and SK-Mel-28 in concentrations up to 20 µM but had moderate cytotoxicity to RPMI-7951 cells with an IC50 of 13 µM. Both investigated substances inhibited the proliferation, formation, and growth of cell colonies of RPMI-7951. PRACTICAL APPLICATIONS: AKG exhibit a variety of biological activities, including anticancer effects. In this study, the liver lipids of the skate B. parmifera and the hepatopancreas lipids of crab P. camtschaticus were shown to be sources of AKG. Our data showed that AKG can be used to prevent the formation of new colonies of malignant cells in combination therapy against melanoma. The results will be useful for future studies involving marine ether lipids and the examination of their anticancer properties against malignant cells.

Cultivation of a thermophilic ammonia oxidizing archaeon synthesizing crenarchaeol.

The widespread occurrence and diversity of ammonia oxidizing Archaea suggests their contribution to the nitrogen cycle is of global significance. Their distribution appeared limited to low- and moderate-temperature environments until the recent finding of a diagnostic membrane lipid, crenarchaeol, in terrestrial hot springs. We report here the cultivation of a thermophilic nitrifier ('Candidatus Nitrosocaldus yellowstonii'), an autotrophic crenarchaeote growing up to 74 degrees C by aerobic ammonia oxidation. The major core lipid of this archaeon growing at 72 degrees C is crenarchaeol, providing the first direct evidence for its synthesis by a thermophile. These findings greatly extend the upper temperature limit of nitrification and document that the capacity for ammonia oxidation is broadly distributed among the Crenarchaeota.

Intact membrane lipids of "Candidatus Nitrosopumilus maritimus," a cultivated representative of the cosmopolitan mesophilic group I Crenarchaeota.

In this study we analyzed the membrane lipid composition of "Candidatus Nitrosopumilus maritimus," the only cultivated representative of the cosmopolitan group I crenarchaeota and the only mesophilic isolate of the phylum Crenarchaeota. The core lipids of "Ca. Nitrosopumilus maritimus" consisted of glycerol dialkyl glycerol tetraethers (GDGTs) with zero to four cyclopentyl moieties. Crenarchaeol, a unique GDGT containing a cyclohexyl moiety in addition to four cyclopentyl moieties, was the most abundant GDGT. This confirms unambiguously that crenarchaeol is synthesized by species belonging to the group I.1a crenarchaeota. Intact polar lipid analysis revealed that the GDGTs have hexose, dihexose, and/or phosphohexose head groups. Similar polar lipids were previously found in deeply buried sediments from the Peru margin, suggesting that they were in part synthesized by group I crenarchaeota.

[Chemical constituents from the south China sea gorgonian coral Subergorgia reticulata].

Nine compounds, cholesterol (1), ergostra-7,22-diene-3beta, 5alpha, 6beta-triol (2), cholesta-7,22-diene-3beta, 5alpha, 6beta-triol (3),5,8-epidioxycampesta-6,22-dien-3-o1 (4), batyl alcohol (5), theine (6), thymine (7), uracil (8), guanine (9), were isolated from the South China Sea gorgonian coral Subergorgia reticulata and their structures elucidated on the basis of spectral data. All of these compounds were isolated for the first time from this gorgonian coral.

Cytotoxic constituents of the octocoral Dendronephthya gigantea.

A known monoalkyl glycerol ether, (+/-)-1-nonadecyloxy-2,3-propanediol (1) was isolated from the ethyl acetate extract of a soft coral Dendronephthya gigantea as a weakly cytotoxic constituent against four human cancer cell lines, A549, HT-29, HT-1080, and SNU-638. In addition, a known ceramide, (2S,3R,4E,8E)-N-hexadecanoyl-2-amino-4,8-octadecadiene-1,3-diol (2), was also isolated as an inactive constituent. This is the first report on the isolation of the compounds 1 and 2 from the octocoral, Dendronephthya species.

Isolation, chemical characterization, and subcellular distribution of 1-O-alkyl-2-acetyl-sn-glycerol in Tetrahymena pyriformis cells.

1-O-Hexadecyl-2-acetyl-sn-glycerol, the immediate precursor of platelet- activating factor (PAF) in its de novo formation, was detected in the protozoon Tetrahymena pyriformis. It was purified from the total lipid extract by TLC, after successive developments in two different solvent systems. Characterization was assessed by (a) gas-liquid chromatography with electron capture detection, and (b) gas chromatography combined with mass spectrometry in selected ion monitoring mode, after derivatization with heptafluorobutyric acid anhydride and tert-butyldimethylchlorosilane/imidazole, respectively. Its quantity was found to be 0.1 nmol/10(7) cells from the GC-MS, using authentic alkylacetylglycerol as external standard. Cell fractionation revealed that alkylacetylglycerol is located exclusively in the microsomal fraction of the protozoon. Previously, we have reported the occurrence of PAF in the microsomal fraction, as well as a dithiothreitol-insensitive CDP-choline: cholinephosphotransferase activity that utilizes exogenous alkylacetylglycerol as substrate in the mitochondrial and microsomal fractions. The above findings indicate that PAF can be formed in the cell by the de novo pathway.

A mixed ladderane/n-alkyl glycerol diether membrane lipid in an anaerobic ammonium-oxidizing bacterium.

A novel glycerol diether containing ladderane and tetradecyl moieties has been identified in an anaerobic ammonium-oxidizing bacterium by GC/MS and high-field NMR spectroscopy.

Biomass measurement of methane forming bacteria in environmental samples.

Methane-forming bacteria contain unusual phytanylglycerol ether phospholipids which can be extracted from the bacteria in sediments and assayed quantitatively by high performance liquid chromatography (HPLC). In this procedure the lipids were extracted, the phospholipids recovered, hydrolyzed, purified by thin layer chromatography, derivatized and assayed by HPLC. Ether lipids were recovered quantitatively from Methanobacterium thermoautotrophicum and sediments at levels as low as 8 x 10(-14) moles. In freshwater and marine sediments the flux of methane to the atmosphere and the methane levels in the pore water reflects the recovery of the phytanyl glycerol ether lipid 'signature'. The proportion of the ether phospholipid to the total recoverable phospholipid was highest in anaerobic digester sewage sludge and deeper subsurface freshwater sediment horizons.

Alkyl glycerol monoethers in the marine sponge Desmapsamma anchorata.

1-O-Hexadecylglycerol (chimyl alcohol), 1-O-heptadecylglycerol and 1-O-octadecylglycerol (batyl alcohol) have been identified as the major native constituents of a mixture of free alkyl glycerol ethers isolated from the contained water and the methanolic extract of the sponge Desmapsamma anchorata. Minor components were the free C14, C15, C19, C20 and C21 alkyl glycerol monoethers. The alkyl glycerol monoethers were analyzed and identified by gas chromatography/mass spectrometry of their isopropylidene derivatives. This is the first report on the occurrence of free C15, C19, C20 and C21 alkyl glycerol monoethers in a sponge.

Characterization of caldarchaetidylglycerol analogs, dialkyl-type and trialkyl-type, from Thermoplasma acidophilum.

The structures of three kinds of phospholipids (PL-X, PL-Y, and PL-T) isolated from Thermoplasma acidophilum have been characterized. The core lipid of PL-Y was caldarchaeol, and that of PL-X was archaeol. The composition of the hydrocarbon chains of the PL-T core lipid was C20 phytane and C40 isoprenoid in a molar ratio of 2 to 1. The major molecular species of the C40 isoprenoid was acyclic without the cyclopentane ring. These three kinds of intact phospholipids commonly had glycerophosphate residues as polar head groups. The structure of PL-T was characterized as trialkyl-type caldarchaetidylglycerol, PL-Y as caldarchaetidylglycerol, and PL-X as archaetidylglycerol.

Purification and characterization of deep sea shark Centrophorus squamosus liver oil 1-O-alkylglycerol ether lipids.

The 1-O-alkylglycerol composition of the liver oil of the deep sea shark Centrophorus squamosus, a species which provides edible flesh, has been determined. After various fractionations of the oil, the unsaponifiable fraction was characterized by means of gas chromatography/mass spectrometry, electron impact, and positive-ion chemical ionization. The oil is composed of 60% unsaponifiable matter, containing 45% squalene, 4.5% cholesterol, and 10% of linear saturated and monounsaturated glycerol ethers with 14-18 carbon atoms. After a first separation by chromatography on silicic acid, monounsaturated glycerol ethers have been separated from the saturated homologues, in particular from 1-O-octadecylglycerol (batyl alcohol) and 1-O-hexadecylglycerol (chimyl alcohol), via urea complexation. This newer application of the urea method, already used in the past to extract saturated from polyunsaturated fatty acids, allowed the purification of the main components of the complex unsaturated glycerol ether fraction, namely, 1-O-octadecen-9'ylglycerol (selachyl alcohol) and 1-O-hexadecen-9'ylglycerol.

Unsaturated glycerol monoethers as novel skin penetration enhancers.

A mixture of glycerol monoethers was extracted from the liver oil of deep sea shark (Centroporus squamosus). It consisted mainly of monoethers of glycerol and linear monounsaturated octadecanol, and glycerol and linear monounsaturated hexadecanol. Only about 11% of the extract consisted of glycerol monoethers derived from linear saturated fatty alcohols. The glycerol monoether extract was somewhat less effective as skin penetration enhancer than oleic acid and other potent fatty acid penetration enhancers, but it was still a very effective enhancer in the hairless mouse skin model used in this study.

[Chemical constituents of Eupolyphaga sinensis Walker].

Five compounds were isolated from the n-hexane extract and n-butanol of extract Eupolyphaga sinensis. These compounds were identified as octacosanol, beta-sitosterol, batyl alcohol, 2,4-pyrimidinedione and allantoin.

[Isolation and identification of chemical constituents from Acropora pulchra].

Three compounds, N-1-(hydroxymethyl)-2-hydroxyl-(E,E)-3,7-heptadecadienal-hexadecanamide(1), batyl alcohol(2) and n-cetanol(3) were isolated from the EtOAc portion of the ethanol extract of the hard coral Acropora pulchra collected from north China sea, and their structures were determined by MS, 1HNMR, 13CNMR analysis.