Chain Mono Research Articles

Preparative regio- and stereoselective α-hydroxylation of medium chain mono- and dicarboxylic fatty acids

Regio- and stereoselective functionalisation reactions like C–H oxidation are of high importance for instance for the valorization of renewables like fatty acids by α-hydroxylation.

FRI056 Effect Of 48 Hour Of Metreleptin In Humans With Lipodystrophy During Controlled Feeding

Abstract Disclosure: K.M. Bukhari: None. B. Abel: None. R.J. Brown: None. Introduction: The lipodystrophy (LD) syndromes are a rare group of disorders characterized by a generalized or partial loss of adipose tissue resulting in a deficiency of the adipocyte-secreted hormone leptin. Leptin replacement therapy with recombinant human leptin (metreleptin) has favorable effects on the metabolic profile of patients with LD and has been shown to have significant effects on metabolic pathways such as fatty acid oxidation and protein degradation following several months of treatment. However, many of these changes may relate to negative energy balance. Whether these changes can be seen within a few days of initiating metreleptin under energy balance conditions is unknown. Objectives: To explore acute (48 hour) and sub-acute (12 days) metabolomic effects of metreleptin under energy balance conditions in human subjects with leptin deficiency due to LD. Methods: The study included 17 patients with LD (5 generalized LD, 12 partial LD) who were studied on a metabolic ward with food intake held constant to maintain energy balance for 2 weeks. Metreleptin 5 mg q12 hr was administered, and fasting blood samples were collected at baseline (T0), after 2 days of treatment (T2), and after 12 days (T12). Untargeted metabolomic (848 compounds) and lipidomic (984 compounds) analysis was completed with the goal of assessing for any physiologically relevant changes during a period of controlled food intake and prior to any clinically relevant changes in dyslipidemia and diabetes. Statistical analyses between time points were done by paired t-tests. To account for false positives, a false discovery rate (q-value) was calculated for each compound, and only those with P≤0.05 are reported. Results: There was a very consistent reduction in the plasma levels of nearly all lipids detected (except monoacylglycerols) at T2 and T12 compared to T0. This includes plasma levels of phospholipids, ceramides, sphingomyelins, cholesterol esters, diacylglycerols (DAG) and triacylglycerols (TAG). There are significantly lower levels at T12 compared to T2 as well, indicating a continued decrease over time. A number of free fatty acids were significantly lower in the T2 metreleptin treated group compared to T0, with a smaller number that were also lower at T12. These included the medium chain, long chain saturated (palmitate [16:0]), long chain mono- and polyunsaturated (nisinate [24:6n3]). In conjunction with this, the levels of acylcarnitines are lower as well. Other significant changes included evidence of increased aerobic glycolysis with increased demand for pyruvate into the TCA cycle, as well as possible increased branched-chain amino acid catabolism with increased input into the TCA cycle. Conclusion: The effects of metreleptin on metabolism in LD appear to be rapid (48 hours), increase further after 12 days, and are independent from longer term changes in food intake, diabetes, and dyslipidemia. Presentation: Friday, June 16, 2023

Cytotoxic Alkylynols of the Sponge Cribrochalina vasculum: Structure, Synthetic Analogs and SAR Studies.

A series of twenty-three linear and branched chain mono acetylene lipids were isolated from the Caribbean Sea sponge Cribrochalina vasculum. Seventeen of the compounds, 1–17, are new, while six, 18–23, were previously characterized from the same sponge. Some of the new acetylene-3-hydroxy alkanes 1, 6, 7, 8, 10 were tested for selective cytotoxicity in non-small cell lung carcinoma (NSCLC) cells over WI-38 normal diploid lung fibroblasts. Compound 7, presented clear tumor selective activity while, 1 and 8, showed selectivity at lower doses and 6 and 10, were not active towards NSCLC cells at all. The earlier reported selective cytotoxicity of some acetylene-3-hydroxy alkanes (scal-18 and 23), in NSCLC cells and/or other tumor cell types were also confirmed for 19, 20 and 22. To further study the structure activity relationships (SAR) of this group of compounds, we synthesized several derivatives of acetylene-3-hydroxy alkanes, rac-18, scal-S-18, R-18, rac-27, rac-32, R-32, S-32, rac-33, rac-41, rac-42, rac-43, rac-45, rac-48 and rac-49, along with other 3-substituted derivatives, rac-35, rac-36, rac-37, rac-38, rac-39 and rac-40, and assessed their cytotoxic activity against NSCLC cells and diploid fibroblasts. SAR studies revealed that the alcohol moiety at position 3 and its absolute R configuration both were essential for the tumor cell line selective activity while for its cytotoxic magnitude the alkyl chain length and branching were of less significance.

Exploring impact of supersaturated lipid-based drug delivery systems of celecoxib on in vitro permeation across PermeapadⓇ membrane and in vivo absorption

Supersaturated lipid-based drug delivery systems have recently been investigated for oral administration for a variety of lipophilic drugs and have shown either equivalent or superior oral bioavailability compared to conventional non-supersaturated lipid-based drug delivery systems. The aim of the present work was to explore supersaturated versus non-supersaturated lipid-based systems at equivalent lipid doses, on in vivo bioavailability in rats and on in vitro permeation across a biomimetic PermeapadⓇ membrane to establish a potential in vivo - in vitro correlation. A secondary objective was to investigate the influence of lipid composition on in vitro and in vivo performance of lipid systems. Results obtained indicated that increasing the celecoxib load in the lipid-based formulations by thermally-induced supersaturation resulted in increased bioavailability for medium and long chain mono-/di-glycerides systems relative to their non-supersaturated (i.e. 85%) reference formulations, albeit only significant for the medium chain systems. Long chain systems displayed higher celecoxib bioavailability than equivalent medium chain systems, both at supersaturated and non-supersaturated drug loads. In vitro passive permeation of celecoxib was studied using both steady-state and dynamic conditions and correlated well with in vivo pharmacokinetic results with respect to compositional effects. In contrast, permeation studies indicated that flux and percentage permeated of supersaturated systems, either at steady-state or under dynamic conditions, decreased or were unchanged relative to non-supersaturated systems. This study has shown that by using two cell-free PermeapadⓇ permeation models coupled with rat-adapted gastro-intestinal conditions, bio-predictive in vitro tools can be developed to be reflective of in vivo scenarios. With further optimization, such models could be successfully used in pharmaceutical industry settings to rapidly screen various prototype formulations prior to animal studies.

Development and optimization of self-nanoemulsifying drug delivery systems (SNEDDS) for curcumin transdermal delivery: an anti-inflammatory exposure

The purpose of this work is to develop novel lipid-based self-nanoemulsifying drug delivery systems (SNEDDS) as carriers for transdermal delivery of curcumin. SNEDDS containing black seed oil, medium chain mono- and diglycerides and surfactants, were prepared as curcumin delivery vehicles. Their formation spontaneity, morphology, droplet size, and drug loading were evaluated. Gel preparation containing two of the SNEDDS formulations were used in the carrageenan induced paw edema to evaluate the anti-inflammatory effect. Results showed droplet size as low as 71 nm. The highest drug loading was observed with SNEDDS-F6 of ∼45 mg/g. In in-vivo investigation, SNEDDS-F6 exhibited significant anti-inflammatory activities in terms of 80% reduction in paw edema when compared with positive control. The prepared SNEDDS with the elevated entrapment efficiency, good transdermal penetration ability could be a suitable candidate for effective transdermal curcumin skin delivery.

Digestion fates of different edible oils vary with their composition specificities and interactions with bile salts

The digestion fates of different edible oils are different. The objective of this study was to understand the influences of lipid composition on their digestion fates, and investigate the roles of bile salts (BS) played in emulsified lipid system (whey protein isolate as emulsifier) in the in-vitro small intestine digestion stage. Three typical oils (palm oil (PO), rapeseed oil (RO) and linseed oil (LINO)) were chosen. Results showed that with the BS addition increased from 0.0 to 2.0 mg/mL, the increasing magnitude of the different fatty acid (FA) apparent release rate constants were: PO > RO ≈ LINO. Although the maximum FA release extent changed with BS addition, the order were: PO > RO > LINO. These may probably be attributed to palmitic acids, the most abundant FA in PO, was mostly located on the Sn-1, 3 positions of triacylglycerol (TAG) molecules, which contributed to the pancreatic lipase hydrolysis action. The relatively short chain length and the lower hydrophobicity also favored this process. However, Sn-1, 3 positions of TAGs in RO and LINO were mainly long chain mono- or poly-unsaturated FAs, which restricted the continuous lipid hydrolysis. Furthermore, the lipid composition may also affect the BS behavior on the O/W emulsion droplet surface, thus modulating lipase hydrolysis reaction. These findings can provide some basic understandings of the digestion differences of different oils.

Composition of Volatile Fraction from Inflorescences and Leaves of Dendrobium moschatum (Orchidaceae)

The volatile fractions from fresh inflorescences and leaves of Dendrobium moschatum (Buchanan-Hamilton) Swartz (Orchidaceae) were isolated by steam distillation with a yield of 0.498% and 0.041% (weight/fresh weight basis), respectively. From GC/FID and GC/MS analyses, coumarin was identified to be the most abundant constituent and quantified as 48.8% and 47.8% of the total volatiles from inflorescences and leaves, respectively. Hydrocarbons, ketones, esters, acids and aldehydes were also detected. Long chain mono unsaturated hydrocarbons were quantified in higher amount in leaves and their structures were elucidated by GC/MS of their dimethyl disulfide derivatives. These compounds together with long chain ethyl esters and methyl ketones may represent a particular feature of this plant species and can play a critical role in the interaction with pollinator insect.

Evaluation of Basic Quality Parameters with in Sunflower and Saff Flower Varieties from Holeta, Ethiopia

Proximate analyses of the sunflower and safflower variety were carried out using AOAC Method and fatty acid profile was analyzed using Gas chromatograph mass spectrometer The result showed that Rassian Black was highest percentage of fat and Protein The fatty acid composition Turkana was the highest Linoleic C Compared to Oissa and Rassian Black Rassian Black was the highest percentage of long chain mono unsaturated fatty acid oleic acid C content compared to oissa and Turkana The sunflower and safflower variety with high linoleic and oleic fatty acid and low saturated fatty acids palmitic C margaric C and stearic C appeared to be suitable for edible oil processer for edible purpose

Organic micropollutants (OMPs) oxidation by ozone: Effect of activated carbon on toxicity abatement

Oxidation and removal of organic micropollutants (OMPs) on ultrapure (UPW) and natural water (NW) by ozone (O3) and ozone/powdered activated carbon (O3/PAC) have been studied. The OMPs atrazine (ATZ, herbicide), carbamazepine (CBZ, anticonvulsant), diclofenac (DCL, anti-inflammatory) and triclosan (TCS, antimicrobial) are incorporated continuously and uncontrolled on water treatment systems (e.g., drinking water treatment plants, wastewater treatment plants).Batch experiments on ultrapure and natural water showed that ATZ treated with O3 and O3/PAC has the slowest transformation rate (>90% at 30min reaction) while CBZ, DCL and TCS were oxidized very fast (>90% at ~5min). The radical scavenger tert-Butyl alcohol (TBA) was used to evaluate the contribution of HO on the OMPs oxidation. TBA, a hydrophilic compound with low adsorbability, was used as a strong HO scavenger to assess the role of the OH radical in the oxidation of the OMPs studied. ATZ oxidation was mainly driven by OH radicals. On the contrary, CBZ, DCL and TCS were removed by direct reaction with ozone. Infrared analysis (FTIR) showed changes in the PAC surface functional groups of the carbon exposed to ozone, decreasing its basic properties.The acute toxicity assays of the OMPs mixture dissolved in UPW performed with D. magna was significantly reduced by ozonation. The addition of PAC to the ozonation process, strongly improved the acute toxicity removal. Short chain mono- and di-carboxylic acids were identified as some of the oxidation intermediates formed during ozone treatment.

Pharmacokinetics of Abamectin/Levamisole Combination in a Medium Chain Mono and Diglyceride-Based Vehicle and an In Vitro Release and In Vitro In Vivo Correlation Study for Levamisole.

A combination of lipophilic and hydrophilic drugs in a single solution is a challenge due to their different physicochemical properties. In vitro and in vivo release studies are useful to optimize this solution. The in vitro (Franz diffusion cell) release rate of levamisole phosphate from an isotropic vehicle of medium chain mono and diglycerides (MCMDG) was significantly slower than the release from water. The injectable solution of the isotropic MCMDG-based system was prepared with 13.65% of levamisole phosphate and 0.5% of abamectin. Two milliliters/50kg (0.04ml/kg) was injected subcutaneously into five healthy adult sheep. None of the animals showed the signs of inflammation at injection site. Both drugs were assayed using validated HPLC methods. The absorption rates for levamisole (0.71 ± 0.32h-1) and abamectin (0.24 ± 0.08day-1) from the MCMDG-based formulation were considerably slower than those of other studies conducted on the commercial products. The tmax was delayed for levamisole (2.20 ± 0.45h) and abamectin (4.20 ± 1.64days) compared with those in published studies. Longer MRT values for levamisole (6.14 ± 1.14h) and abamectin (8.80 ± 1.39days) were found in this study compared to those reported. A correlation was observed between in vivo fraction absorbed and in vitro fraction released for levamisole phosphate in the MCMDG-based formulation. The injection vehicle of isotropic MCMDG-based system delayed the subcutaneous absorption of levamisole phosphate and abamectin compared to the commercial subcutaneous injection products for levamisole and abamectin. Notably, this isotropic MCMDG-based vehicle system is prepared with a combination of two drugs with different physicochemical properties.

Functional self-assembled lipidic systems derived from renewable resources.

Self-assembled lipidic amphiphile systems can create a variety of multi-functional soft materials with value-added properties. When employing natural reagents and following biocatalytic syntheses, self-assembling monomers may be inherently designed for degradation, making them potential alternatives to conventional and persistent polymers. By using non-covalent forces, self-assembled amphiphiles can form nanotubes, fibers, and other stimuli responsive architectures prime for further applied research and incorporation into commercial products. By viewing these lipid derivatives under a lens of green principles, there is the hope that in developing a structure-function relationship and functional smart materials that research may remain safe, economic, and efficient.

高純度長鎖モノアルキルリン酸塩の特異な会合挙動

界面活性剤などの両親媒性物質が形成する自己組織体は学術的にも工業的にも利用価値が高く、多くの研究がなされている。近年、従来は不安定であると考えられていたαゲルが多くの注目を集め、様々な研究が行われている。 我々も新たにαゲルを構築しうる素材の開発を進め、その結果、モノアルキル純度を高めたアルキルリン酸が中和剤の選択により非常に安定なαゲルを構築することを見出した。 本稿では特に化粧品分野で行われてきたαゲルの研究例を示しながら、我々が見出したαゲル形成素材について述べる。

直鎖型モノアルキルリン酸エステルの特異な会合挙動と化粧品への応用

直鎖型モノアルキルリン酸エステルの特異な会合挙動と化粧品への応用

Mixed lipid phase SMEDDS as an innovative approach to enhance resveratrol solubility

Context: Despite its promising therapeutic activities, clinical use of resveratrol (RSV) is compromised with unfavorable biopharmaceutical properties, namely low water solubility.Objective: This work deals with improving RSV solubility and release rate through its incorporation in innovative mixed lipid phase self-microemulsifying drug delivery systems (SMEDDS).Methods: (Pseudo)ternary diagrams were constructed for different oils and surfactant mixtures. Selected systems were further evaluated for RSV solubility, self-emulsification ability, accelerated stability, dynamic viscosity, compatibility with hard gelatin capsules and in vitro dissolution of RSV.Results: Lipid phase composed of diverse lipid species, castor oil (long-chained triglyceride) and Capmul MCM (mixture of medium chain mono and diglycerides) allowed formulation of mixed lipid SMEDDS with lower surfactants content (60% Cremophor EL/RH 40/RH 60). Mixed lipid phase SMEDDS showed best self-emulsifying ability with regard to self-emulsifying time as well as droplet size and monodispersity of microemulsions obtained upon SMEDDS dilution with aqueous phase. Overall, incorporation of RSV in SMEDDS resulted in improved solubility (over 23-fold) and dissolution rate compared to crystalline RSV. All SMEDDS formulations were adequately viscous for filling into hard gelatin capsules (>150 mPaċs for empty SMEDDS; >400 mPaċs for RSV-loaded SMEDDS) and no leaking was observed during three months of storage.Conclusion: The presented work indicates the promising potential of mixed lipid SMEDDS formulations for future development of SMEDDS with lower surfactant content and no added cosolvents for incorporation of RSV and other poorly soluble drugs.

Examination of benzoquinone electrooxidation pathway as crucial step of phenol degradation process

The electrochemical oxidation of benzoquinone on expanded graphite (EG) electrode was conducted. Electrochemical process was realized by cyclic voltammetry technique in alkaline solution. The main part of this work was devoted to examination of benzoquinone oxidation proceeding through the opening of aromatic ring accompanied by the formation of carboxylic acids. Water samples containing benzoquinone and short chain mono- and dicarboxylic acids were analyzed qualitatively and quantitatively with high performance liquid chromatography (HPLC). The validation of chromatographic method was determined for benzoquinone, oxalic acid, malonic acid, acetic acid, maleic acid, succinic acid and fumaric acid.

Myosin light chain mono- and di-phosphorylation differentially regulate adhesion and polarity in migrating cells

Myosin II is a critical regulator of cell migration that generates polarity, controls protrusion, and promotes adhesion maturation and retraction of the rear. Myosin II has an ATPase motor domain that is regulated by phosphorylation of the regulatory light chain (RLC) on Thr18 and Ser19. Here, we address the activation and specific function of the two phosphorylation states of the RLC, mono- (S19) and/or di-phosphorylation (T18 + S19), in cell polarity and adhesion. Specific phospho-antibodies reveal that adhesion to fibronectin via the α5β1 integrin promotes localized mono- and di-phosphorylation of the RLC that follow different kinetics. Using phospho-mimetic mutants, we show that mono-phosphorylation promotes adhesion maturation in protrusions resulting in focal adhesions throughout the cell. In contrast, di-phosphorylation produces large, stable actomyosin bundles and large, non-dynamic adhesions that define the rear. Finally, RLC phosphorylation regulates the assembly and stability of MIIB, but not MIIA. Our data reveal a novel mechanism by which the degree of phosphorylation of the RLC differentially controls cell adhesion and polarity.

Peroxisomal Plant 3-Ketoacyl-CoA Thiolase Structure and Activity Are Regulated by a Sensitive Redox Switch

The breakdown of fatty acids, performed by the beta-oxidation cycle, is crucial for plant germination and sustainability. beta-Oxidation involves four enzymatic reactions. The final step, in which a two-carbon unit is cleaved from the fatty acid, is performed by a 3-ketoacyl-CoA thiolase (KAT). The shortened fatty acid may then pass through the cycle again (until reaching acetoacetyl-CoA) or be directed to a different cellular function. Crystal structures of KAT from Arabidopsis thaliana and Helianthus annuus have been solved to 1.5 and 1.8 A resolution, respectively. Their dimeric structures are very similar and exhibit a typical thiolase-like fold; dimer formation and active site conformation appear in an open, active, reduced state. Using an interdisciplinary approach, we confirmed the potential of plant KATs to be regulated by the redox environment in the peroxisome within a physiological range. In addition, co-immunoprecipitation studies suggest an interaction between KAT and the multifunctional protein that is responsible for the preceding two steps in beta-oxidation, which would allow a route for substrate channeling. We suggest a model for this complex based on the bacterial system.

Bitumen fluxing properties of a new class of sustainable solvents: The isosorbide di-alkyl ethers

The performances of new bio-sourced solvents, the short chain mono- and di-alkyl isosorbide ethers, have been determined and compared to benchmark bitumen fluxes. The influences of fluxes and temperature on the Newtonian viscosity have been assessed. The various fluxes appear to impact also on the visco-elastic behaviour of paving bitumen and dimethyl isosorbide ether (DMI) exhibits good fluxing properties. This bio-sourced solvent has also the property to be fully miscible with water. The bitumen hardness recovery can consequently occur from two different phenomena: evaporation and diffusion from the bitumen to water, making this solvent an appropriate bitumen flux for rainy seasons.

Fabrication and photophysical property of Tb(III), Dy(III) and Eu(III) complex LB films containing double functional ligand of long chain mono docosyl phthalate

In this paper, new novel long chain amphiphillic monoester molecules were designed to afford double functions: film-formation and luminescent sensitization. Subsequently, organized molecular films of rare earth complexes with the functional ligands formulated as ML 2NO 3 were fabricated by the Langmuir–Blodgett film (LB) technology, where M denotes rare earth ions Eu 3+, Tb 3+ and Dy 3+; L denotes the long chain carboxylic ligands monodocosyl phthalate (22-Phth). The average molecular area was obtained according to the π-A isotherms. The LB film layer structure was demonstrated by low-angle X-ray diffraction and the average layer spacing were obtained according to the Bragg equation. UV absorbance intensity increases linearly with the number of LB films layers, which indicate that the LB films are homogeneously deposited. The fluorescence spectra of these LB films were quite different from those of their corresponding solid complexes. It reveals that the long chain esters ligands are suitable for those of the excited states of the luminescent Tb 3+ ion and Dy 3+ ion in the LB films as well as in the solid complexes, but not sensitize the europium ion effectively in the LB films.

Fabrication and spectroscopic properties of Langmuir–Blodgett films of novel zinc complexes with long chain mono (hexadecyl, octadecyl, eicosyl, and docosyl) phthalate

In this paper, some novel long chain amphiphillic monoester molecules were designed to afford double functions: film-formation and luminescent sensitization. Subsequently, organized molecular films of zinc complexes with these functional ligands formulated as ZnL 2 were fabricated by the Langmuir–Blodgett film (LB) technology, where L denoted the long chain carboxylic ligands monohexadecyl phthalate (16-Phth), monooctadecyl phthalate (18-Phth), monoeicosyl phthalate (20-Phth) and monodocosyl phthalate (22-Phth). The average molecular area was obtained according to the π–A isotherms. The layer structure of the LB films was demonstrated by low-angle X-ray diffraction and the average layer spacing were obtained according to the Bragg equation. The characteristic luminescence behaviors of LB films have been discussed compared with those of their corresponding solid complexes.