- Large-scale synthesis of both symmetrical and unsymmetrical triacylglycerols containing docosahexaenoic acid
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A large-scale (～100 g) synthesis of symmetrical and unsymmetrical triacylglycerols containg docosahexaenoic acid (D) and two of either lauric (L), palmitic (P) or stearic acid (S) is described. Key improvements in purification of synthetic intermediates, in addition to a more efficient acetonide cleavage reaction affords the six TAGs (LaDLa, LaLaD, PDP, PPD, SDS, SSD) in yields of 80-90% and in regioisomeric purities greater than or equal to 90%.
- Andrews, Philip C.,Fraser, Benjamin H.,Junk, Peter C.,Massi, Massimiliano,Perlmutter, Patrick,Thienthong, Neeranat,Wijesundera, Chakra
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- Facile access to arsenic-containing triacylglycerides
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The previously unknown arsenic-containing triacylglycerides (AsTAGs) 3-((15-(dimethylarsinoyl)pentadecanoyl)oxy)propane-1,2-diyl dipalmitate 1 and 2-((15-(dimethylarsinoyl)pentadecanoyl)oxy)propane-1,3-diyl dipalmitate 2 have been synthesized. They will serve as model compounds in the search for naturally occurring AsTAGs, recently proposed natural constituents of fish oils.
- Guttenberger, Nikolaus,Sagmeister, Peter,Glabonjat, Ronald A.,Hirner, Stefan,Francesconi, Kevin A.
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- Use of glycerol carbonate in an efficient, one-pot and solvent free synthesis of 1,3-sn-diglycerides
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An efficient solvent-free synthesis of a variety of highly pure 1,3-sn-diglycerides (1,3-sn-diacylglycerols) in a two-step one pot process is described. Heating glycerol carbonate (4-hydroxymethyl-1,3-dioxolan-2-one) with fatty acid anhydrides 2a-d affords 1:1 mixtures of glycerol carbonate fatty esters 3a-3d and the corresponding fatty acids. Further heating the reaction mixtures in the presence of catalytic amounts of 1,4-diazabicyclo[2.2.2]octane (DABCO) at 195-200 °C yields highly pure 1,3-sn-diglycerides 4a-4d.
- Kargar, Mojgan,Hekmatshoar, Rahim,Ghandi, Mehdi,Mostashari, Abdoljalil
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- Synthesis and biological evaluation of two glycerolipidic prodrugs of didanosine for direct lymphatic delivery against HIV
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Novel glycerolipidic prodrugs of didanosine and didanosine monophosphate designed to by-pass the hepatic first pass metabolism were synthesized and tested for their cytotoxicity and anti-HIV-1 activity. Formulation as liposomes of dipalmitoylphosphatidylcholine was elaborated. A simple quantitative HPLC-UV method was developed and validated, and ESI-MS was used for qualitative purpose. These two prodrugs exhibited promising biological activities against HIV-1 in in vitro infected cell culture.
- Lalanne, Muriel,Paci, Angelo,Andrieux, Karine,Dereuddre-Bosquet, Nathalie,Clayette, Pascal,Deroussent, Alain,Re, Micheline,Vassal, Gilles,Couvreur, Patrick,Desmaele, Didier
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- Diglyceride prodrug strategy for enhancing the bioavailability of norfloxacin
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Prodrug approach using diglyceride as a promoiety is a promising strategy to improve bioavailability of poorly absorbed drugs and the same was explored in the present work to improve oral bioavailability of norfloxacin; a second generation fluoroquinolone antibacterial. The prodrug was synthesized by standard procedures using dipalmitine as a carrier and the structure was confirmed by spectral analysis. Higher Log P indicated improved lipophilicity. The ester linkage between norfloxacin and dipalmitine would be susceptible to hydrolysis by lipases to release the parent drug and carrier in the body. In vivo kinetic studies in rats indicated 53% release of norfloxacin in plasma at the end of 8 h. The prodrug exhibited improved pharmacological profile than the parent compound at equimolar dose that indirectly indicated improved bioavailability.
- Dhaneshwar, Suneela,Tewari, Kunal,Joshi, Sonali,Godbole, Dhanashree,Ghosh, Pinaki
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- LIPID PRODRUGS OF PREGNANE NEUROSTEROIDS AND USES THEREOF
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The present invention provides lymphatic system-directing lipid prodrugs, pharmaceutical compositions thereof, methods of producing such prodrugs and compositions, as well as methods of improving the bioavailability or other properties of a therapeutic agent that comprises part of the lipid prodrug. The present invention also provides methods of treating a disease, disorder, or condition such as those disclosed herein, comprising administering to a patient in need thereof a disclosed lipid prodrug or a pharmaceutical composition thereof.
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- LIPID PRODRUGS OF JAK INHIBITORS AND USES THEREOF
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The present invention provides lymphatic system-directing lipid prodrugs, pharmaceutical compositions thereof, methods of producing such prodrugs and compositions, and methods of improving the bioavailability or other properties of a therapeutic agent that comprises part of the lipid prodrug. The present invention also provides methods of treating a disease, disorder, or condition such as those disclosed herein, comprising administering to a patient in need thereof a disclosed lipid prodrug or a pharmaceutical composition thereof.
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- LIPID PRODRUGS OF BTK INHIBITORS AND USES THEREOF
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The present invention provides lymphatic system-directing lipid prodrugs, pharmaceutical compositions thereof, methods of producing such prodrugs and compositions, and methods of improving the bioavailability or other properties of a therapeutic agent that comprises part of the lipid prodrug. The present invention also provides methods of treating a disease, disorder, or condition such as those disclosed herein, comprising administering to a patient in need thereof a disclosed lipid prodrug or a pharmaceutical composition thereof.
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- LIPID PRODRUGS OF GLUCOCORTICOIDS AND USES THEREOF
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The present invention provides lymphatic system-directing lipid prodrugs, pharmaceutical compositions thereof, methods of producing such prodrugs and compositions, and methods of improving the bioavailability or other properties of a therapeutic agent that comprises part of the lipid prodrug. The present invention also provides methods of treating a disease, disorder, or condition such as those disclosed herein, comprising administering to a patient in need thereof a disclosed lipid prodrug or a pharmaceutical composition thereof.
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- MODULATORS OF INDOLEAMINE 2,3-DIOXYGENASE
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Provided are IDO1 inhibitor compounds of Formula I and pharmaceutically acceptable salts thereof, their pharmaceutical compositions, their methods of preparation, and methods for their use in the prevention and/or treatment of diseases. Formula I Wherein R1 is a group having Formula II
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(2019/07/19)
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- Discovery of FAHFA-Containing Triacylglycerols and Their Metabolic Regulation
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FAHFAs are a class of bioactive lipids, which show great promise for treating diabetes and inflammatory diseases. Deciphering the metabolic pathways that regulate endogenous FAHFA levels is critical for developing diagnostic and therapeutic strategies. However, it remains unclear how FAHFAs are metabolized in cells or tissues. Here, we investigate whether FAHFAs can be incorporated into other lipid classes and identify a novel class of endogenous lipids, FAHFA-containing triacylglycerols (FAHFA-TGs), which contain a FAHFA group esterified to the glycerol backbone. Isotope-labeled FAHFAs are incorporated into FAHFA-TGs when added to differentiated adipocytes, which implies the existence of enzymes and metabolic pathways capable of synthesizing these lipids. Induction of lipolysis (i.e., triacylglycerol hydrolysis) in adipocytes is associated with marked increases in nonesterified FAHFA levels, demonstrating that FAHFA-TGs breakdown is a regulator of cellular FAHFA levels. To quantify FAHFA levels in FAHFA-TGs and determine their regioisomeric distributions, we developed a mild alkaline hydrolysis method that liberates FAHFAs from triacylglycerols for easier detection. FAHFA-TG concentrations are greater than 100-fold than that of nonesterified FAHFAs, indicating that FAHFA-TGs are a major reservoir of FAHFAs in cells and tissues. The discovery of FAHFA-TGs reveals a new branch of TG and FAHFA metabolism with potential roles in metabolic health and regulation of inflammation.
- Tan, Dan,Ertunc, Meric Erikci,Konduri, Srihari,Zhang, Justin,Pinto, Antonio M.,Chu, Qian,Kahn, Barbara B.,Siegel, Dionicio,Saghatelian, Alan
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supporting information
p. 8798 - 8806
(2019/06/11)
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- LYMPHATIC SYSTEM-DIRECTING LIPID PRODRUGS
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The present invention provides lymphatic system-directing lipid prodrugs, pharmaceutical compositions thereof, methods of producing such prodrugs and compositions, as well as methods of improving the bioavailability or other properties of a therapeutic agent that comprises part of the lipid prodrug. The present invention also provides methods of treating a disease, disorder, or condition such as those disclosed herein, comprising administering to a patient in need thereof a provided lipid prodrug or a pharmaceutical composition thereof.
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- Triglyceride prodrug based on lymphatic mediated transport and preparation method thereof
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The invention belongs to the technical field of medicines, and relates to a triglyceride prodrug based on lymphatic mediated transport, in particular to a triglyceride prodrug with different linkagesand based on lymphatic mediated transport and preparation and application of the triglyceride prodrug in drug delivery. The present invention provides the prodrug with different connecting keys and asynthesis method thereof. The structure of the prodrug is as follows, and X, R1, R2, n and m are described in the claims and specifications. According to the prodrug provided by the invention, the digestion and absorption mechanism of glycerol in the gastrointestinal tract is simulated by using the structure of triglycerides, the lymphatic transport of drugs is promoted, the first-pass effect is avoided, and the prodrug has targeting property and can obviously enhance or improve the bioavailability of drugs.
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- Highly efficient solvent-free synthesis of 1,3-diacylglycerols by lipase immobilised on nano-sized magnetite particles
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Recently, 1,3-DAGs (1,3-diacylglycerols) have attracted considerable attention as healthy components of food, oil and pharmaceutical intermediates. Generally, 1,3-DAG is prepared by lipase-mediated catalysis in a solvent free system. However, the system's high reaction temperature (required to reach the reactants' melting point), high substrate concentration and high viscosity severely reduce the lipase's activity, selectivity and recycling efficiency. In this report, MjL (Mucor javanicus lipase) was found to have the best performance in the solvent-free synthesis of 1,3-DAGs of several common commercial lipases. By covalent binding to amino-group-activated NSM (nano-sized magnetite) particles and cross-linking to form an enzyme aggregate coat, MjL's specific activity increased 10-fold, and was able to be reused for 10 cycles with 90% residual activity at 55 °C. 1,3-DAGs of lauric, myristic, palmitic, stearic, oleic and linoleic acid were prepared using the resulting immobilised enzyme, all with yields greater than 90%, and the reaction time was also greatly reduced.
- Meng, Xiao,Xu, Gang,Zhou, Qin-Li,Wu, Jian-Ping,Yang, Li-Rong
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p. 319 - 324
(2013/10/08)
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- Study of surfactant alcohols with various chemical moieties at the hydrophilic-hydrophobic interface
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The melting behavior, the solubility, and the influence of hydrogen bonds were analyzed for a series of single- and double-tailed surfactant alcohols. Various effects such as the presence of free amides or the intermolecular spacing were found to be important factors for increasing or decreasing the melting temperature of a surfactant. Furthermore, we present a model for the packing of diamido-lipids and study the temperature-dependence of the IR signals. The Royal Society of Chemistry 2013.
- Zaffalon, Pierre-Leonard,D'Anna, Vincenza,Hagemann, Hans,Zumbuehl, Andreas
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p. 7237 - 7244
(2013/07/05)
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- 13C NMR quantification of mono and diacylglycerols obtained through the solvent-free lipase-catalyzed esterification of saturated fatty acids
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In the present investigation, we studied the enzymatic synthesis of monoacylglycerols (MAG) and diacylglycerols (DAG) via the esterification of saturated fatty acids (stearic, palmitic and an industrial residue containing 87% palmitic acid) and glycerol in a solvent-free system. Three immobilized lipases (Lipozyme RM IM, Lipozyme TL IM and Novozym 435) and different reaction conditions were evaluated. Under the optimal reaction conditions, esterifications catalyzed by Lipozyme RM IM resulted in a mixture of MAG and DAG at high conversion rates for all of the substrates. In addition, except for the reaction of industrial residue at atmospheric pressure, all of these products met the World Health Organization and European Union directives for acylglycerol mixtures for use in food applications. The products were quantified by 13C NMR, with the aid of an external reference signal which was generated from a sealed coaxial tube filled with acetonitrile-d3. After calibrating the area of this signal using the classical external reference method, the same coaxial tube was used repeatedly to quantify the reaction products. Copyright
- Fernandes, Jane Luiza Nogueira,De Souza, Rodrigo Octavio Mendonca Alves,De Vasconcellos Azeredo, Rodrigo Bagueira
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experimental part
p. 424 - 428
(2012/08/14)
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- BODP - A versatile reagent for phospholipid synthesis
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Benzyloxydichlorophosphine (BODP) has been found to be a convenient reagent for the synthesis of phospholipids. A series of artificial ether and ester phospholipids have been prepared in good to high yields. Georg Thieme Verlag Stuttgart New York.
- Zaffalon, Pierre-Leonard,Zumbuehl, Andreas
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experimental part
p. 778 - 782
(2011/04/22)
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- Crystallization and polymorphism of 1,3-acyl-palmitoyl-rac-glycerols
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Crystallization and melting behavior, small-angle X-ray scattering, X-ray powder diffraction and infra-red absorbance were measured for nine 1,3-acyl-palmitoyl-rac-glycerols (1,3-acetoyl-, -butyroyl-, -hexanoyl-, -octanoyl-, -decanoyl-, -lauroyl, -myristoyl- and -oleoyl-palmitoyl-rac-glycerol and 1,3-dipalmitoyl-glycerol). All but one of the prepared 1,3-diacylglycerols (1,3-DAG) were β-stable with 1,3-acetoyl-palmitoyl-rac-glycerol being the exception (β-stable). Small-angle X-ray scattering indicates that molecules in β-tending diacid 1,3-DAG adopt a herringbone-type configuration similar to monoacid 1,3-DAG. In this configuration acyl chains of the same length associate and regular chain-end matching between terminal methyl groups delineate lamellae. In contrast, molecules in crystalline 1,3-acetoyl-palmitoyl- rac-glycerol are oriented similar to those of 1(3)-monoacylglycerol. Interestingly, DSC curves indicate five of the nine diacid compounds have meta-stable forms-suggesting these forms are quite common for diacid 1,3-DAG. Meta-stable forms are observed in the melting curve when the difference in length between acyl chains is large (1,3-acetoyl-, -butyroyl- and -hexanoyl-palmitoyl-rac-glycerol), and in the crystallization curve when the difference is moderate (1,3-decanoyl- and -lauroyl-palmitoyl-rac-glycerol).
- Craven, R. John,Lencki, Robert W.
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experimental part
p. 1113 - 1123
(2011/11/07)
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- Preparation of diacid 1,3-diacylglycerols
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A complete methodology (including synthesis, purification and analysis) for the preparation of 1,3-DAG is described. For a successful synthesis project, the strengths and weaknesses of each particular process should be taken into account and measures taken to offset or balance potential weaknesses. To this end, we describe some of the challenges associated with: chemically and enzymatically catalyzed acylglycerol syntheses; recrystallization and flash chromatography for purification of partial acylglycerols; and thin-layer chromatography (TLC) separation of DAG. For this work, 1-MAG intermediates and subsequent diacid 1,3-DAG were prepared using non-enzymatic methods, whereas, monoacid 1,3-DAG were prepared by enzymatic methods. It was not always possible to obtain pure samples of target compounds-in recrystallizations this is due to solid solution formation and co-crystallization and in chromatographic separations it is due to co-elution of components with similar Rf. Furthermore, TLC Rf of DAG is determined by two main factors: acyl chain length and positional isomerism. Interestingly, while the role of positional isomerism is well-known, the role of acyl chain length in these separations has only recently come to light.
- Craven, R. John,Lencki, Robert W.
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experimental part
p. 1281 - 1291
(2011/08/21)
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- Enzymatic synthesis of monoglycerides by esterification reaction using Penicillium camembertii lipase immobilized on epoxy SiO2-PVA composite
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Glycerol-fatty acid esterification has been conducted with lipase from Penicillium camembertii lipase immobilized on epoxy SiO2-PVA in solvent-free media, with the major product being 1-monoglyceride, a useful food emulsifier. For a given set of initial conditions, the influence of reaction was measured in terms of product formation and selectivity using different fatty acids as acyl donors. Results were found to be relatively dependent of the chain length of the fatty acids, showing high specificity for both myristic and palmytic acids attaining final mixture that fulfills the requirements established by the World Health Organization to be used as food emulsifiers.
- Freitas, Larissa,Paula, Ariela V.,dos Santos, Julio C.,Zanin, Gisella M.,de Castro, Heizir F.
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experimental part
p. 87 - 90
(2010/10/19)
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- Synthesis and physical properties of symmetrical and non-symmetrical triacylglycerols containing two palmitic fatty acids
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A series of symmetrical (ABA) and non-symmetrical (AAB) triacylglycerol (TAG) isomers containing "A," palmitic (P; 16:0) acid, and "B," either oleic (O; 9c-18:1), elaidic (E; 9t-18:1), linoleic (L; 9c,12c-18:2) or linolenic (Ln; 9c,12c,15c-18:3) fatty acids were synthesized by esterification of the thermodynamically more-stable 1,3-di- or 1(3)-monoacylglycerols [1,3-DAG or 1(3)-MAG], respectively. 1,3- dipalmitoylglycerol (1,3P-DAG) was esterified with O, L or Ln acid to prepare the symmetrical TAG isomers POP, PLP and PLnP, while the O- E-, L- and Ln-1(3)MAG precursors, synthesized or obtained commercially, were esterified with P acid to prepare the non-symmetrical TAG isomers OPP, EPP, LPP and LnPP, respectively. The drop point(s), solid fat content and melting point values of the synthesized TAG were determined. The 1,3-dipalmitoylglycerol (1,3P-DAG) and 1(3)P-MAG precursors were prepared, in multi-gram quantities, by partial glycerolysis (glycerol/p-toluenesulfonic acid) of tripalmitin. After fractionation by silica gel chromatography, the 1(3)P-MAG and 1,3P-DAG isomers (ca. 80% of total MAG or DAG) were purified (>98%) by crystallization from acetone [silver ion-HPLC was utilized to determine the structural purities of the DAG (or MAG) precursors, and the synthesized TAG]. Esterification of the appropriate, thermodynamically more-stable MAG or DAG precursors was found to be a very versatile method for synthesis (in 80-90% yields) of multi-gram (3-5 g) quantities of symmetrical and non-symmetrical TAG isomers, in chemical and structural purities of >96 and 97-99%, respectively.
- Adlof,List
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- Practical syntheses of triacylglycerol regioisomers containing long-chain polyunsaturated fatty acids
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Docosahexaenoic acid (DHA, 22:6n-3) is known to protect against a range of degenerative disease conditions and aid in the development of eye and brain function in infants. In dietary lipids DHA is found primarily in the triacylglycerol (TAG) form. However, the effects of the positional distribution of DHA in TAG on lipid functional properties such as bioactivity and oxidative stability are not clearly understood. Studies on this subject for the most part are limited by a lack of regioisomerically pure TAG model compounds containing DHA or similar long-chain (LC)-polyunsaturated fatty acids (PUFA). This paper reports on the development of a practical procedure, based on chemical and enzymatic reactions, for the syntheses of regioisomerically enriched, symmetrical and unsymmetrical TAG isomers containing two palmitic acid and one of linoleic acid, linolenic acid, or DHA. 1,3-Selective acylation of glycerol with vinyl esters of fatty acids catalyzed by Candida antarctica lipase and direct coupling with fatty acids in the presence of the coupling agents 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 4-dimethylaminopyridine furnished 1,3-dihexadecanoyl-2-docosahexaenoyl glycerol and its unsymmetrical isomer 1,2-dihexadecanoyl-3-docosahexaenoyl glycerol in 99 and 60% yield, respectively. Critical to the success of the unsymmetrical TAG synthesis is the demonstration that PUFA-containing glycerol acetonides can readily survive appropriately tailored acid-catalyzed conditions. In this way, sufficient quantities of highly regioisomerically enriched PUFA-containing unsymmetrical monoacylglycerols (MAG) and TAG have now become routinely accessible. The methods are amenable to scale-up and could be adopted for regioenriched synthesis of a wide range of TAG. AOCS 2007.
- Fraser, Benjamin H.,Perlmutter, Patrick,Wijesundera, Chakra
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- Therapeutic use of of acyglycerols and the nitrogen-and sulphur-containing analogues thereof
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The invention relates to the use of acylglycerols and the nitrogen- and sulfur-containing analogues thereof in therapy, particularly for the treatment of cerebral ischemia. The invention further relates to methods for preparing said derivatives, novel compounds, in particular acylglycerols, the nitrogen- and sulfur-containing analogues thereof and methods for preparing same.
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(2010/11/24)
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- Therapeutic use of acyl glycerols and the nitrogen- and sulphur- containing analogues thereof
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The invention relates to the use of acyl glycerols and the nitrogen- and sulfur-containing analogues thereof in the therapeutic field, particularly in human health. The inventive compounds have advantageous pharmacological properties and are particularly of use for the prevention or treatment of neurodegenerative diseases.
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(2008/06/13)
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- Synthesis, pharmacological activity and hydrolytic behavior of glyceride prodrugs of ibuprofen
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For reducing the gastrointestinal toxicity associated with ibuprofen its carboxylic group was condensed with the hydroxyl group of 1,2,3-trihydroxy propane 1,3-dipalmitate/stearate to give the ester prodrugs 3a and 3b. The release of ibuprofen from these prodrugs has been studied at pH 3, 4, 5 and 7.4 by HPLC using methanol and 0.05% phosphoric acid (80%) (70:30) as mobile phase. The prodrugs showed insignificant hydrolysis at pH 5 compared to pH 7.4 indicating that the prodrugs do not break in stomach but release ibuprofen at pH 7.4 in adequate amounts. In vivo hydrolysis studies in rats, the peak plasma concentration of ibuprofen was attained in 1.5:h in case of ibuprofen and in 2:h in prodrugs treated animals. The plasma concentration was found to be less at all times in animals treated with ibuprofen compared to the prodrugs treated animals. The maximum anti-inflammatory activity of ibuprofen was observed at 2 h whereas prodrugs showed maximum activity at 3 h and remained practically constant upto 8:h whereas a decrease in activity was observed with free ibuprofen. Further the prodrugs showed less gastric ulcers compared to ibuprofen. An average score of 0.16, 0.45, 0.97 and 0.20, 0.76, 1.02 of ulcers was observed with 3a and 3b compared to an average score of 0.75, 1.10, and 2.97 with ibuprofen. These prodrugs also showed significant protection against acetic acid induced writhings in rats. These finding suggested that both the prodrugs are better in action as compared to the parent drug and are advantageous in having less gastrointestinal side effects.
- Khan,Akhter, Mymoona
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p. 371 - 376
(2007/10/03)
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- HYDROLASES, NUCLEIC ACIDS ENCODING THEM AND MEHODS FOR MAKING AND USING THEM
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The invention provides hydrolases, polynucleotides encoding them, and methods of making and using these polynucleotides and polypeptides. In one aspect, the invention is directed to polypeptides, e.g., enzymes, having a hydrolase activity, e.g., an esterase, acylase, lipase, phospholipase (e.g., phosphlipase A, B, C and D acitvity, patatin activity, lipid acyl hydrolase (LAH) activity) or protease activity, including thermostable and thermotolerant hydrolase activity, and polynucleotides encoding these enzyme, and making and using these polynucleotides and polypeptides. The hydrolase activities of the polypeptides and peptides of the invention include esterase activity, lipase activity (hydrolysis of lipids), acidolysis reactions (to replace an esterified fatty acid with a free fatty acid), transesterification reactions (exchange of fatty acids between triglycerides), ester synthesis, ester interchange reactions, phospholipase activity and protease activity (hydrolysis of peptide bonds). The polypeptides of the invention can be used in a variety of pharmaceutical, agricultural and industrial contexts, including the manufacture of cosmetics and nutraceuticals. In another aspect, the polypeptides of the invention are used to synthesize enantiomerically pure chiral products.
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(2008/06/13)
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- A new sunscreen of the cinnamate class: Synthesis and enzymatic hydrolysis evaluation of glyceryl esters of p-methoxycinnamic acid
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Glyceryl esters of p-methoxycinnamic acid, 1,3-dipalmitoyl-2-p- methoxycinnamoyl-1,2,3-propanetriol and 1,3-dioctanoyl-2-p-methoxycinnamoyl-1,2, 3-propanetriol were synthesised in an attempt to increase substantivity and decrease eventual undesirable effects of sunscreens of this class. To assess if the glyceryl esters could present a higher stability towards hydrolysis by lipases in the stratum corneum, hydrolysis rates were determined in vitro using a commercial fungal lipase from Rhizomucor miehei. Results presented herein show that the glyceryl esters have similar λmax and ε values to sunscreens of the cinnamate class. The ester 1,3-dipalmitoyl-2-p- methoxycinnamoyl-1,2,3-propanetriol presented a 2.8 times lower hydrolysis rate by lipase, in vitro, than the commercial sunscreen 2-ethylhexyl-p- methoxycinnamate (alkyl ester). This finding suggests that this triacylglycerol can possibly have a longer retention time in the skin and consequently promote a more intense and effective antisolar action than the commercial sunscreen.
- De Freitas, Zaida Maria Faria,Dos Santos, Elisabete Pereira,Da Rocha, Joao Ferreira,Dellamora-Ortiz, Gisela Maria,Goncalves, Jose Carlos Saraiva
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- Conversion of a carboxylesterase into a triacylglycerol lipase by a random mutation
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A true convert: The carboxylesterase enzyme R.34 (see picture) can be converted into a triacylglycerol lipase without modification of the shape, size, or hydrophobicity of the substrate binding site. The substitution of Asn33 by Asp results in a salt bridge between the Asp33 and Arg49, which causes a distortion of the enzyme structure that makes the catalytic site more accessible to larger substrates but also more labile. (Figure Presented).
- Reyes-Duarte, Dolores,Polaina, Julio,Lopez-Cortes, Nieves,Alcalde, Miguel,Plou, Francisco J.,Elborough, Kieran,Ballesteros, Antonio,Timmis, Kenneth N.,Golyshin, Peter N.,Ferrer, Manuel
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p. 7553 - 7557
(2007/10/03)
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- Design of well balanced hydrophilic-lipophilic catalytic surfaces for the direct and selective monoesterification of various polyols
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The transesterification process is a well known reaction of organic chemistry. However, the monoesterification of unprotected polyols such as glycerol or sucrose is much more complex and the design of selective catalysts is becoming a huge challenge in order to avoid many protection and deprotection steps, harmful for the cost and the environmental impact of the resulting process. In this study, we showed that the control of the hydrophilic-lipophilic balance of heterogeneous catalysts is a crucial key in order to tune both the catalyst activity and the monoester selectivity. Indeed, whereas homogeneous guanidine led to low selectivity toward monoesters, its anchorage on a hydrophilic solid support such as silica allowed us to prepare two basic hybrid organic-inorganic materials able to selectively afford monoesters in high yield and in an environmentally-friendly process, at low temperature and starting from an equimolecular mixture of unprotected polyols and various fatty methyl esters. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2005.
- Kharchafi, Ghizlane,Jerome, Francois,Adam, Isabelle,Pouilloux, Yannick,Barrault, Joel
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p. 928 - 934
(2007/10/03)
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- Fatty acid compounds, preparation and uses thereof
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The invention concerns novel molecules, their preparation and their uses, in particular in the field of human and veterinary medicine and cosmetics. The inventive compounds are partly fatty acid derivatives and exhibit advantageous pharmacological and cosmetic properties. The invention also concerns various uses of said compounds, the pharmaceutical compositions containing them and methods for preparing them. The inventive compounds are useful in particular for preventing and/or treating dyslipidemiae, cardiovascular diseases, syndrome X, restenosis, diabetes, obesity, hypertension, certain cancers, dermatological diseases and in cosmetics, for fighting against skin aging and its effects notably against wrinkles and the like
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- Chemoenzymatic synthesis of structured triacylglycerols by highly regioselective acylation
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A highly efficient two-step chemoenzymatic synthesis of structured triacylglycerols comprising a pure n-3 polyunsaturated fatty acid at the mid-position and a pure saturated fatty acid located at the end-positions is described. In the first step an immobilized Candida antarctica lipase was observed to display an excellent regioselectivity toward the end-positions of glycerol at 0-4°C using vinyl esters as acylating agents. The n-3 fatty acids were introduced into the remaining mid-position highly efficient and in excellent yields using EDCI coupling agent.
- Halldorsson, Arnar,Magnusson, Carlos D.,Haraldsson, Gudmundur G.
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p. 9101 - 9109
(2007/10/03)
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- Preparative synthesis of 1,2- and 1,3-disubstituted phosphatidic acids
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A general preparative method for the synthesis of 1,2(3)-diacyl and 1-alkyl-2(3)-acyl phosphatidic acids by examples with acyl = C15H31CO and alkyl = C16H33 was proposed. The procedure involved two stages: the interaction of 1,2- or 1,3-disubstituted glycerols with POCl3 at 0-3°C leading to the corresponding phosphodichlorides, and their hydrolysis with 80% aqueous DMSO or DMF at room temperature. The corresponding phosphatidic acids were isolated in the form of pyridinium salts in approximately 80% yields. In the absence of DMSO or DMF, the hydrolysis of 1-hexadecyl-2-palmitoyl 3-glycerophosphodichloride with aqueous pyridine resulted in an admixture of P,P′-bis(1-hexadecyl-2-palmitoyl)-3-glyceryl pyrophosphate (10-30 mol %) along with the corresponding phosphatidic acid. This admixture also yielded the target phosphatidic acid upon hydrolysis in aqueous DMSO. 1999 MAEe Cyrillic signK "Hayκa/Interperiodica".
- Khromova,Malekin,Kisin,Nosova,Kruglyak,Kurochkin
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p. 268 - 272
(2007/10/03)
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- Synthesis and evaluation of the anti-inflammatory effects of niflumic acid lipophilic prodrugs in brain edema
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Five new lipophilic prodrugs of the non-steroidal anti-inflammatory drug, niflumic acid (Nifluril, CAS 4394-00-7), were synthetized and evaluated on the experimental brain edema (injection of phospholipase A2). The effect of these drugs in comparison with dexamethasone which elicits a marked effect on clinical and experimental brain edema was evaluated. Niflumic acid was vectorised by cholesterol, hexadecanol and by three 1,3-diacylglycerols. The anti-inflammatory activity of these compounds on experimental brain edema was evaluated by determination of the prostaglandin E2 (PGE2) brain tissue concentration. Niflumic acid reduced the prostaglandin E2 production more significantly than dexamethasone. Niflumic acid prodrug forms (1,3-dihexadecanoyl-2-[2-[3-(trifluoromethyl)anilino]nicotinoyl]glycer ol and 1,3-dihexadecanoyl-2-[2-[3-(trifluoromethyl)anilino]nicotinoyloxybutan oyl]glycerol also showed a marked anti-inflammatory activity at low concentrations.
- El Kihel, Laila,Bourass, Jilali,Richomme, Pascal,Petit, Jean Yves,Letourneux, Yves
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p. 1040 - 1044
(2007/10/03)
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- Interesterification Kinetics of Triglycerides and Fatty Acids with Modified Lipase in n-Hexane
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The kinetics of lipase-catalyzed interesterification of triglycerides and fatty acids in organic media was studied.First, the lipase Saiken 100, Rhizopus japonicus, was modified by surfactant to form an enzyme precipitate in aqueous solution, which was well dispersed in organic solvents.This modified lipase catalyzed the interesterification of tripalmitin and stearic acid.The enzyme has 1,3-positional specificity and does not distinguish between stearic and palmitic acids.The kinetic model developed to describe the interesterification reaction system is based on mass balance of two consecutive second-order reversible reactions.The reaction rate constant, k, was determined by solving the differential rate equations of the reaction system and by expressing the value of k as a function of concentrations of the substrates with time.The model gave satisfactory results.The best value of the specific reaction rate constant k* that fits all experimental data was 1.2*10-5 2/(mmol*mg biocatalyst*h)> under the reaction conditions in this study. Key words: Acidolysis, biocatalyst, fatty acids, interesterification kinetics, modified lipase, palmitic acid, reaction rate constant, stearic acid, triglycerides.
- Basheer, Sobhi,Mogi, Ken-ichi,Nakajima, Mitsutoshi
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p. 511 - 518
(2007/10/02)
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- Synthesis of the orally macrofilaricidal and stable glycerolipidic prodrug of melphalan, 1,3-dipalmitoyl-2-(4'(bis(2''-chloroethyl)amino)phenylalaninoyl)glycer ol
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A new strategy is presented to develop macrofilaricidal compounds orally administered and able to concentrate in the lymphatic system. A diglyceride derivative of melphalan, 1,3-dipalmitoyl-2-(4'(bis(2''-chloroethyl]amino) phenylalaninoyl) glycerol, was synthesized. The esterification of melphalan by 1,3-dipalmitin allowed chemical stabilization of the alkylating agent in aqueous dispersion. No degradation of this prodrug was observed after a 3 month storage of an aqueous dispersion at 4°C. The filaricidal activity of the prodrug was compared with those of melphalan in vitro against adults, infective larvae and microfilariae of Molinema dessetae, and evaluated in vivo on Molinema dessetae infected Proechimys oris. In vitro, melphalan and the glycerolipidic prodrug were inactive against microfilariae but active at 1 mmol/l against infective larvae and adults. In vivo studies were performed with rodents subcutaneously inoculated with infective larvae from Aedes aegypti. The number of macrofilariae was significantly reduced following treatment with a single oral dose of the alkylating agent prodrug (0.082 mmol/kg).
- Deverre,Loiseau,Puisieux,Gayral,Letourneux,Couvreur,Benoit
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p. 1153 - 1156
(2007/10/02)
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- Topical corticosteroid formulations
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This present invention relates to a solution for topical or local application comprising at least one corticosteroid; from about 1% to 4% by weight of solubilization agents consisting essentially of a combination of at least one glyceryl ester of a fatty acid of 6 to 22 carbon atoms and a betaine surfactant, from about 10% to 50% by weight of composition of an alkanol cosolvent, and from about 20% to 50% water.
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- Preparation of glyceride esters
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The invention concerns the preparation of glycerides in which glycidol is reacted with a fatty acid, first in the form of the anhydride to produce the corresponding epoxy glyceride or glycidol ester, at the same time liberating free fatty acid from the anhydride and thereafter continuing reaction, this time between the liberated free fatty acid or another acid, in the presence of an acylation catalyst under the influence of which the oxirane ring is ruptured and diglycerides produced. These may be used in the preparation of synthetic fats.
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- Coal tar gel composition
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Compositions effective for topically treating skin conditions, especially psoriasis and eczema which contains as an essential ingredient coal tar in a gel base.
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- Glycerides with anti-inflammatory properties
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Triglycerides carrying hydrocarbon acyl moieties in the 1- and 3-positions and the 2-methyl-1,3-benzodioxan-4-on-2-yl moiety in the 2-position exhibit excellent anti-inflammatory properties.
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