- Long-lived and highly conducting ion channels formed by lipophilic ethylenediamine palladium(ii) complexes
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The synthesis of a lipophilic ethylenediamine palladium(ii) complex and its activity in planar bilayer membranes are reported. In acetonitrile solution containing one equivalent of 4,4-bipyridine the complex forms the expected metallosupramolecular tetrameric square. The same mixture provokes transmembrane conductance of three types: an initial period of erratic behavior, occasional short channel-like openings, and frequent very long-lived and highly conducting channel openings. The apparent pore radii of both short and long openings vary continuously over the range of 0.1-1.5 nm, and long-lived pores will form in the absence of 4,4′-bipyridine. The long-lived channels are presumed to involve an extended aggregate of the palladium complex and lipids surrounding a toroidal pore in the membrane. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.
- Fyles, Thomas M.,Tong, Christine C.
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Read Online
- NUCLEIC ACID OF FORMULA (I): GlXmGn, OR (II): ClXmCn, IN PARTICULAR AS AN IMMUNE-STIMULATING AGENT/ADJUVANT
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The present invention relates to a nucleic acid of the general formula (I): GlXmGn, or (II): ClXmCn, which may be modified by a lipid. The nucleic acid of the invention acts as an immune-stimulating agent inducing the innate immune response. The invention relates further to a pharmaceutical composition (in a first embodiment), each containing an immune-stimulating agent according to the invention in combination with a pharmaceutically active carrier/vehicle (and, optionally, further auxiliary substances, additives and/or further adjuvants). In another embodiment, the inventive nucleic acid is combined with at least one pharmaceutically active component, a pharmaceutically acceptable carrier/vehicle (and, optionally, further auxiliary substances, additives and/or further adjuvants). Accordingly, the present invention is directed to a vaccine, which corresponds to a pharmaceutical composition of the invention (second embodiment), wherein the pharmaceutically active component induces a specific immune response (e.g. an antigen). The present invention relates likewise to the use of a nucleic acid of the invention or a pharmaceutical composition according to the invention for the treatment of infectious diseases, autoimmune diseases, allergies or cancer diseases.
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Paragraph 0231-0237
(2020/02/05)
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- Synthesis of natural 1- O -alkylglycerols: A study on the chemoselective opening of the epoxide ring by onium quaternary salts (N and P) and ionic liquids
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A chemoselective route for the synthesis of 1-O-alkylglycerols chimyl (1), batyl (2), and selachyl (3) is reported. These compounds can be naturally isolated from shark liver oil and the skin of animals such as stingrays and chimeras and exhibit potential anti-fouling activity. The synthetic approach developed in this work included two distinct methods of preparation. The first was based on solvent-free reactions catalyzed by onium quaternary salts (N and P) and ionic liquids; the second methodology was based on a series of one-pot reactions.
- Nascimento, Thiana Santiago,Braga, Esther Faria,Casaes Gomes, Giselle Cristina,Batista, William Rom?o,Mazzei Albert, André Luís,Capella Lopes, Rosangela Sabbatini,Lopes, Claudio Cerqueira
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p. 1050 - 1054
(2020/01/23)
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- Design, synthesis and cytotoxicity of chimeric erlotinib-alkylphospholipid hybrids
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Two series of erlotinib-alkylphospholipid hybrids were prepared and evaluated for their antiproliferative activities against a panel of four cell lines representing lung, breast, liver and skin cancers using erlotinib and miltefosine as reference standards. Amide analogs elicited more enhanced cytotoxic activity than analogous esters. Amide derivatives 8d and 8e exhibited promising broad-spectrum antiproliferative activity and higher efficacy than reference erlotinib and miltefosine. Their cellular GI50 values was in the ranges of 24.7–46.9 μM and 26.8–43.1 μM for 8e and 8d respectively. Assay results of the inhibitory activity of the prepared compounds on EGFR kinase reaction and Akt phosphorylation in conjugation with statistical correlation analysis indicated that other mechanisms might contribute to their elicited cytotoxicities. In addition, statistical correlation analysis revealed that mechanisms of elicited cytotoxicities for amide series might be different from ester series. In addition, correlation analysis indicated variations in the mechanisms according to the types of cell line.
- Alam, Md. Maqusood,Hassan, Ahmed H.E.,Lee, Kun Won,Cho, Min Chang,Yang, Ji Seul,Song, Jiho,Min, Kyung Hoon,Hong, Jongki,Kim, Dong-Hyun,Lee, Yong Sup
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supporting information
p. 51 - 62
(2018/11/27)
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- Synthesis of alkyl-glycerolipids standards for gas chromatography analysis: Application for chimera and shark liver oils
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Natural O-alkyl-glycerolipids, also known as alkyl-ether-lipids (AEL), feature a long fatty alkyl chain linked to the glycerol unit by an ether bond. AEL are ubiquitously found in different tissues but, are abundant in shark liver oil, breast milk, red blood cells, blood plasma, and bone marrow. Only a few AEL are commercially available, while many others with saturated or mono-unsaturated alkyl chains of variable length are not available. These compounds are, however, necessary as standards for analytical methods. Here, we investigated different reported procedures and we adapted some of them to prepare a series of 1-O-alkyl-glycerols featuring mainly saturated alkyl chains of various lengths (14:0, 16:0, 17:0, 19:0, 20:0, 22:0) and two monounsaturated chains (16:1, 18:1). All of these standards were fully characterized by NMR and GC-MS. Finally, we used these standards to identify the AEL subtypes in shark and chimera liver oils. The distribution of the identified AEL were: 14:0 (20–24%), 16:0 (42–54%) and 18:1 (6–16%) and, to a lesser extent, (0.2–2%) for each of the following: 16:1, 17:0, 18:0, and 20:0. These standards open the possibilities to identify AEL subtypes in tumours and compare their composition to those of non-tumour tissues.
- Pinault, Michelle,Guimaraes, Cyrille,Couthon, Hélène,Thibonnet, Jér?me,Fontaine, Delphine,Chant?me, Aurélie,Chevalier, Stephan,Besson, Pierre,Jaffrès, Paul-Alain,Vandier, Christophe
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- PROCESS FOR PREPARING A POLYOL ETHER
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The present invention relates to a process for preparing a polyol ether of formula (I), comprising a step of reductive alkylation involving a compound of general formula (II) and a compound of general formula (III): in which R1, R2, R3 and R4 are as defined in claim 1.
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Paragraph 0128
(2014/02/16)
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- Selective synthesis of 1-O-Alkyl(poly)glycerol ethers by catalytic reductive alkylation of carboxylic acids with a recyclable catalytic system
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(Poly)glycerol monoethers were synthesized in good yield and selectivity by the catalytic reductive alkylation of glycerol, diglycerol, and triglycerol with readily available, cheap and/or bio-sourced carboxylic acids. The reaction was catalyzed by 1 mol % of Pd/C under 50 bar H2 using an acid ion-exchange resin as a recyclable cocatalyst. The catalytic system was recycled several times, and a mechanism is proposed for this transformation.
- Sutter, Marc,Dayoub, Wissam,Metay, Estelle,Raoul, Yann,Lemaire, Marc
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p. 2397 - 2409
(2013/02/23)
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- PLASMALOGEN COMPOUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME AND METHODS FOR TREATING DISEASES OF THE AGING
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Described herein are routes of synthesis and therapeutic uses of 1-alkyl, 2-acyl glycerol derivatives of formula I: which when administered to mammalian biological systems result in increased cellular concentrations of specific sn-2 substituted ethanolamine plasmalogens independent of the ether lipid synthesis capacity of the system. Elevating levels of the specific sn-2 substituted species in this way can cause lowering of membrane cholesterol levels and the lowering of amyloid secretion. These compounds can be used for the treatment or prevention of diseases of aging associated with increased membrane cholesterol, increased amyloid, and decreased plasmalogen levels, such as neurodegeneration (including Alzheimer''s disease, Parkinson''s disease and age-related macular degeneration), cognitive impairment, dementia, cancer (e.g. prostate, lung, breast, ovarian, and kidney cancers), osteoporosis, bipolar disorder and vascular diseases (such as atherosclerosis, hypercholesterolemia).
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Page/Page column 29; 35
(2010/07/09)
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- OXIDIZED THIOPHOSPHOLIPID COMPOUNDS AND USES THEREOF
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Novel oxidized thiophospholipids are provided herein, as well as methods for producing same, and uses thereof in treating or preventing an inflammation associated with endogenous oxidized lipids and related conditions. Exemplary oxidized thiophospholipid according to embodiments described herein have the formula: (I) wherein X1, X2, A1, A2, B', B'', D' and D'' are as described herein.
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Page/Page column 60-61
(2010/04/28)
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- Nucleic Acid of Formula (I): GIXmGn, or (II): CIXmCn, in Particular as an Immune-Stimulating Agent/Adjuvant
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The present invention relates to a nucleic acid of the general formula (I): GlXmGn, or (II): ClXmCn, which may be modified by a lipid. The nucleic acid of the invention acts as an immune-stimulating agent inducing the innate immune response. The invention relates further to a pharmaceutical composition (in a first embodiment), each containing an immune-stimulating agent according to the invention in combination with a pharmaceutically active carrier/vehicle (and, optionally, further auxiliary substances, additives and/or further adjuvants). In another embodiment, the inventive nucleic acid is combined with at least one pharmaceutically active component, a pharmaceutically acceptable carrier/vehicle (and, optionally, further auxiliary substances, additives and/or further adjuvants). Accordingly, the present invention is directed to a vaccine, which corresponds to a pharmaceutical composition of the invention (second embodiment), wherein the pharmaceutically active component induces a specific immune response (e.g. an antigen). The present invention relates likewise to the use of a nucleic acid of the invention or a pharmaceutical composition according to the invention for the treatment of infectious diseases, autoimmune diseases, allergies or cancer diseases.
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- Sterol-modified phospholipids: Cholesterol and phospholipid chimeras with improved biomembrane properties
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We synthesized a family of sterol-modified glycerophospholipids (SML) in which the sn-1 or sn-2 position is covalently attached to cholesterol and the alternative position contains an aliphatic chain. The SML were used to explore how anchoring cholesterol to a phospholipid affects cholesterol behavior in a bilayer. Notably, cholesterol in the SML retains the membrane condensing properties of free cholesterol regardless of the chemistry or position of its attachment to the glycerol moiety of the phospholipid. SMLs by themselves formed liposomes upon hydration and in mixtures between an SML and diacylglycerophospholipids (C14 to C18 chain length) the thermotropic phase transition is eliminated at the SML equivalent of about 30 mol % free cholesterol. Osmotic-induced contents leakage from SML (C14-C18) liposomes depends upon the linkage and position of cholesterol but in general is similar to that observed in 3/2 diacylphosphatidylcholine/cholesterol (mole ratio) liposomes. SML liposomes are exceptionally resistant to contents release in the presence of serum at 37°C. This is probably due to the fact that SML exchange between bilayers is more than 100 fold less than the exchange rate of free cholesterol in the same conditions. Importantly, SML liposomes containing doxorubicin are as effective in treating the murine C26 colon carcinoma as Doxil, a commercial liposome doxorubicin formulation. SMLs stabilize bilayers but do not exchange and hence provide a new tool for biophysical studies on membranes. They may improve liposomal drug delivery in organs predisposed to the extraction of free cholesterol from bilayers, such as the skin, lung, or blood.
- Huang, Zhaohua,Szoka Jr., Francis C.
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supporting information; experimental part
p. 15702 - 15712
(2009/03/12)
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- ADJUVANT IN THE FORM OF A LIPID-MODIFIED NUCLEIC ACID
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The present invention relates to an immune-stimulating adjuvant in the form of a lipid-modified nucleic acid, optionally in combination with further adjuvants. The invention relates further to a pharmaceutical composition and to a vaccine, each containing an immune-stimulating adjuvant according to the invention, at least one active ingredient and optionally a pharmaceutically acceptable carrier and/or further auxiliary substances and additives and/or further adjuvants. The present invention relates likewise to the use of the pharmaceutical composition according to the invention and of the vaccine according to the invention for the treatment of infectious diseases or cancer diseases. Likewise, the present invention includes the use of the immune-stimulating adjuvant according to the invention in the preparation of a pharmaceutical composition for the treatment of cancer diseases or infectious diseases.
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Page/Page column 24
(2010/11/29)
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- IMPROVED PROCESS FOR THE PREPARATION OF OXIDIZED PHOSPHOLIPIDS
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Novel synthetic routes, which are highly applicable for industrial preparation of therapeutically beneficial oxidized phospholipids are disclosed. Particularly, novel methods for efficiently preparing compounds having a glycerolic backbone and one or more oxidized moieties attached to the glycerolic backbone, which are devoid of column chromatography are disclosed. Further disclosed are novel methods of introducing phosphorous-containing moieties such as phosphate moieties to compounds having glycerolic backbone and intermediates formed thereby.
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Page/Page column 41-42
(2008/06/13)
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- Lipase-catalysed kinetic resolution of 1-O-alkylglycerols by sequential transesterification
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The natural S-configured chimyl, batyl and selachyl alcohols of the 1-O-alkylglycerol type were prepared by enantioselective lipase-catalysed transesterification. Their racemates were synthesised in two steps by reacting racemic solketal with the bromides of the corresponding fatty alcohols and a subsequent conversion of the intermediates into the 1-O-alkylglycerols by deprotection under acidic aqueous conditions. The Pseudomonas fluorescens lipase was employed to kinetically resolve the racemic 1-O-alkylglycerols by a sequential diacetylation process to afford them virtually enantiomerically pure. Dramatic enantioselectivity increase was observed for the saturated chimyl (E = 17-32) and batyl (E = 14-38) alcohols at decreased temperature, whereas for the monounsaturated selachyl (E = 12-13) alcohol no such temperature effects were observed.
- Halldorsson, Arnar,Thordarson, Pall,Kristinsson, Bjorn,Magnusson, Carlos D.,Haraldsson, Gudmundur G.
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p. 2893 - 2899
(2007/10/03)
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- Kinetic resolution of 1-O-alkylglycerols by lipase
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Pseudomonas sp. lipase was employed to resolve kinetically 1-O- alkylglycerols by a sequential diacylation process. Only low or moderate E- values were obtained, but at approximately 60% conversion enantiomerically pure monoacetates were obtained of the natural S-configuration for glyceryl ether lipids.
- Haraldsson, Gudmundur G.,Thordarson, Pall,Halldorsson, Arnar,Kristinsson, Bjorn
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p. 3671 - 3674
(2007/10/03)
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- Influence of α-branched fatty acid chains on the thermotropic behaviour of racemic 1-O-hexadecyl-2-acyl-glycero-3-phosphocholines
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Phosphatidylcholines containing an α-branched palmitic acid ester linked to position C2 of the glycerol backbone were synthesized and characterized using differential scanning calorimetry and X-ray diffraction. As the length of the sidegroup substituted on the palmitic acid chain is changed, the calorimetric parameters pass through a minimum. The polymorphic behaviour is different when the sidegroup is larger, or smaller, than propyl. The comparison of the physicochemical parameters of isomers differing in the bonding of the branched chain fatty acid to the glycerol backbone (to position C1 or C2, respectively) shows that the chains are nonequivalent. Keywords: Phosphatidylcholine; Branched chain fatty acids; Microcalorimetry; X-ray diffraction; Polymorphism
- Rattay, Bernd,Brezesinski, Gerald,Dobner, Bodo,Foerster, Guenter,Nuhn, Peter
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- Synthesis of a 'reverse ester' analogue of 1,2-sn-diglycerides from (S)-1,2-di-O-isoprophylideneglycerol; efficient, stereospecific nucleophilic displacement via a triflate at glycerol C-2
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An optically pure glyceride analogue in which the 2-O-ester grouping has been reversed was efficiently synthesised from (S)-di-O-isopropylideneglycerol by a sequence that featured an SN 2 displacement by the anion of diethyl malonate on a protected glycerol 2-O-triflate.
- Golding, Bernard T.,Griffin, Alice L.,Robinson, David H.
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p. 6459 - 6462
(2007/10/02)
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- Phosphocholine derivative inhibitors of phospholipase A2
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Phospocholine derivatives having the formula: STR1 in which W, Z, Q and R are described in the specification are disclosed as useful for inhibiting the enzyme phospholipase A2. Methods of making and using the compounds are also disclosed.
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- Analogues of Platelet Activating Factor. 6. Mono- and Bis-Aryl Phosphate Antagonists of Platelet Activating Factor
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A series of aryl phosphoglyceride (3, 19-61) and bis-aryl phosphate (67-135) antagonists of platelet activating factor (PAF) were prepared.A group of four bifunctional phosphorus reagents (5a-c and 7) were developed that allowed the preparation of these aryl phosphates in which the position of aromatic substitution can be varied.These compounds were examined for their ability to inhibit PAF-induced platelet aggregation of rabbit platelets.Selected compounds were also evaluated for their ability to displace PAF from its receptor on rabbit platelets.These in vitro data were compared to similar data obtained for a number of known PAF antagonists.The compounds were evaluated in vivo, in both the mouse and rabbit, for their ability to prevent death induced by a lethal challenge of PAF.The relationships between the biological activity and the nature, lipophilicity, and position of substituents of the aromatic rings were studied.Compound 105 (CL 184005) has been selected to undergo further development as a potential therapeutic agent for the treatment of septic shock in man.
- Wissner, A.,Carroll, M. L.,Green, K. E.,Kerwar, S. S.,Pickett, W. C.,et al.
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p. 1650 - 1662
(2007/10/02)
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- Disubstituted tetrahydrofurans and dioxolanes as PAF antagonists
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A new series of disubstituted tetrahydrofuran and dioxolane derivatives were prepared and evaluated for their PAF antagonist activity in the PAF-induced in vitro platelet-aggregation and in vivo hypotension tests. Several of these compounds exhibited more potent activity than the structurally related 2-[N-acetyl-N-[[[[2-methoxy-3-[(octadecylcarbamoyl)oxy]propoxy] carbonyl]amino]methyl]-1-ethylpyridinium chloride (CV-6209, 3) in the in vitro assay, whereas all showed less potency in the in vivo test. The role of both the substituent nature and the placement and number of oxygen atoms in the ring are discussed. A qualitative SAR study was carried out on these nuclei.
- Bartroli,Carceller,Merlos,Garcia-Rafanell,Forn
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p. 373 - 386
(2007/10/02)
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- Synthesis of 1-O-alkyl-2-O-acetyl-Sn-3-glyceryl-3-phosphoryl choline the enantiomer of platelet activating factor (PAF)
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A novel sterospecific synthesis of biologically active ether-phospholipids (PAF) is reported, involving chemoenzymatic approach.
- Kumar,Shanker
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p. 1763 - 1768
(2007/10/02)
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