Cytotoxic Potential of Betulinic Acid Fatty Esters and Their Liposomal Formulations: Targeting Breast, Colon, and Lung Cancer Cell Lines.

Betulinic acid is a lupane-type pentacyclic triterpene mostly found in birch bark and thoroughly explored for its wide range of pharmacological activities. Despite its impressive biological potential, its low bioavailability has challenged many researchers to develop different formulations for achieving better in vitro and in vivo effects. We previously reported the synthesis of fatty acid esters of betulinic acid using butyric, stearic, and palmitic acids (But-BA, St-BA, and Pal-BA) and included them in surfaced-modified liposomes (But-BA-Lip, St-BA-Lip, Pal-BA-Lip). In the current study, we evaluated the cytotoxic effects of both fatty acid esters and their respective liposomal formulations against MCF-7, HT-29, and NCI-H460 cell line. The cytotoxic assessment of BA derivatives revealed that both the fatty esters and their liposomal formulations acted as cytotoxic agents in a dose- and time-dependent manner. But-BA-Lip exerted stronger cytotoxic effects than the parent compound, BA and its liposomal formulation, and even stronger effects than 5-FU against HT-29 cells (IC50 of 30.57 µM) and NCI-H460 cells (IC50 of 30.74 µM). BA's fatty esters and their respective liposomal formulations facilitated apoptosis in cancer cells by inducing nuclear morphological changes and increasing caspase-3/-7 activity. The HET-CAM assay proved that none of the tested compounds induced any irritative effect, suggesting that they can be used safely for local applications.

Chemo-Enzymatic Synthesis and Biological Assessment of p-Coumarate Fatty Esters: New Antifungal Agents for Potential Plant Protection.

One trend in agriculture is the replacement of classical pesticides with more ecofriendly solutions, such as elicitation, which is a promising approach consisting of stimulating the natural immune system of a plant to improve its resistance to pathogens. In this fashion, a library of p-coumaric-based compounds were synthesized in accordance with as many principles of green chemistry as possible. Then, these molecules were tested for (1) the direct inhibition of mycelium growth of two pathogens, Botrytis cinerea and Sclerotinia sclerotiorum, and (2) plasma membrane destabilization in Arabidopsis and rapeseed. Finally, the protective effect was evaluated on an Arabidopsis/B. cinerea pathosystem. Total inhibition of the growth of both fungi could be achieved, and significant ion leakage was observed using dihydroxylated fatty p-coumarate esters. A direct effect on plants was also recorded as a ca. three-fold reduction in the necrosis area.

Impact of chemical structure on the in vitro hydrolysis of fatty esters of 2-ethylhexanoic acid or 2-ethylhexanol and extrapolation to the in vivo situation.

Fatty esters of 2-ethylhexanoic acid (EHA) and 2-ethylhexanol (EH) are commonly used in cosmetics. Human liver and skin S9 and human plasma were used to determine the in vitro rates of clearance (CLint) of a series of compounds, with a range of 2-11 carbons on the acid or alcohol moiety and branching at the C2 position. The impact of carbon chain length on in vitro CLint was most prominent for the liver metabolism of esters of EH, while for in vitro skin metabolism it was greater for esters of EHA. The position of the branching also impacted the liver hydrolysis rates, especially for the C3, C4, and C5 esters with lower CLint in vitro rates for esters of EHA relative to those of EH. When the in vitro intrinsic clearance rates were scaled to in vivo rates of hepatic clearance, all compounds approximated the rate for hepatic blood flow, mitigating this dependence of metabolism on structure. This work shows how structural changes to the molecule can affect in vitro metabolism and, furthermore, allows for an estimation of the in vivo metabolism.

Understanding of the residual odour of fatty esters used as emollient in cosmetic products.

OBJECTIVE: Fatty esters are known for their versatility, but in addition to their performance as emollients, emulsifiers, solubilizers, or dispersing agents, they have to meet more and more criteria to be used in cosmetic products. Thus, their olfactory characteristics are expected to be as neutral as possible. However, despite a step of deodorization during the synthesis of fatty esters, a residual odour is currently still perceived at the end of the process. METHODS: In this study, a specific analytical methodology combining sensory with chemical analyses was implemented to characterize the residual odour of two fatty esters and to determine its origin. Ethyl oleate and isononyl isononanoate were selected and underwent a sensory analysis to evaluate their odour intensity and odour profile. Volatile compounds released by these esters were assessed by GC-MS after solid-phase microextraction and among them, odouractive compounds were brought into light using gas chromatography coupled with mass spectrometry and olfactometry analyses. RESULTS: On the isononyl isononanoate chromatogram, only peaks corresponding to the different isomeric ester forms were evidenced while around 70 volatile compounds were detected in the ethyl oleate headspace, including esters, aldehydes, hydrocarbons, and ketones. Isononyl alcohol used as raw material in the synthesis was proven to be responsible for isononyl isononanoate final odour. As for ethyl oleate, of the 23 odour-active compounds perceived, 14 have been identified; they are mainly esters and saturated as well as unsaturated aldehydes. CONCLUSION: A novel measurement approach was presented to analyse trace odours of fatty esters and the results will be useful to control their deodorization by targeting appropriate strategies with the aim to either avoid the formation or remove the identified odorant compounds. This study may be further expanded by investigating the impact of deodorization on odour-active compounds for a complete understanding of their contribution to the fatty ester global odour.

OBJECTIF: Les esters gras sont connus pour leur polyvalence, mais en plus de leurs performances en tant qu'émollients, émulsifiants, solubilisants ou agents dispersants, ils doivent répondre à de plus en plus de critères pour être utilisés dans les produits cosmétiques. Ainsi, une odeur la plus neutre possible est recherchée par les formulateurs. Cependant, malgré une étape de désodorisation lors de la synthèse, une faible odeur résiduelle est souvent encore perçue à la fin du processus. METHODES: Dans cette étude, une méthodologie analytique spécifique combinant des analyses sensorielles et chimiques a été mise en œuvre pour caractériser l'odeur résiduelle de deux esters gras et déterminer son origine. L'oléate d'éthyle et l'isononanoate d'isononyle ont été sélectionnés et une analyse sensorielle a été menée pour évaluer l'intensité et le profil descriptif de leur odeur. Les composés volatils libérés par ces deux esters ont été identifiés par GC-MS après microextraction en phase solide (SPME) et parmi eux, les composés odorants ont été mis en évidence à l'aide de la chromatographie en phase gazeuse couplée à des analyses de spectrométrie de masse et d'olfactométrie (GC-MS-O). RESULTATS: Sur le chromatogramme de l'isononanoate d'isononyle, seuls des pics correspondant aux différentes formes isomériques de l'ester ont été mis en évidence tandis qu'environ 70 composés volatils ont été détectés dans l'espace de tête de l'oléate d'éthyle, parmi lesquels des esters, des aldéhydes, des hydrocarbures et des cétones. Il a été montré que l'alcool isononylique utilisé comme matière première dans la synthèse était responsable de l'odeur finale de l'isononanoate d'isononyle. Pour l'oléate d'éthyle, sur les 23 composés odorants perçus, 14 ont été identifiés ; il s'agit principalement d'esters et d'aldéhydes saturés ou insaturés. CONCLUSION: Ce travail présente une approche efficace pour analyser les traces d'odeur des esters gras. Les résultats obtenus permettront de contrôler la désodorisation de ces ingrédients cosmétiques en ciblant des stratégies appropriées dans le but d'éliminer spécifiquement les composés odorants identifiés. Cette étude pourra être élargie en étudiant l'impact de la désodorisation sur les composés odorants pour une meilleure compréhension de leur contribution à l'odeur globale des esters gras.

Enzymatic Synthesis of Fatty Acid Isoamyl Monoesters from Soybean Oil Deodorizer Distillate: A Renewable and Ecofriendly Base Stock for Lubricant Industries.

In this study, soybean oil deodorizer distillate (SODD), a mixture of free fatty acids and acylglycerides, and isoamyl alcohol were evaluated as substrates in the synthesis of fatty acid isoamyl monoesters catalyzed by Eversa (a liquid formulation of Thermomyces lanuginosus lipase). SODD and the products were characterized by the chemical and physical properties of lubricant base stocks. The optimal conditions to produce isoamyl fatty acid esters were determined by response surface methodology (RSM) using rotational central composite design (RCCD, 23 factorial + 6 axial points + 5 replications at the central point); they were 1 mol of fatty acids (based on the SODD saponifiable index) to 2.5 mol isoamyl alcohol, 45 °C, and 6 wt.% enzymes (enzyme mass/SODD mass). The effect of the water content of the reactional medium was also studied, with two conditions of molecular sieve ratio (molecular sieve mass/SODD mass) selected as 39 wt.% (almost anhydrous reaction medium) and 9 wt.%. Ester yields of around 50 wt.% and 70 wt.% were reached after 50 h reaction, respectively. The reaction products containing 43.7 wt.% and 55.2 wt.% FAIE exhibited viscosity indices of 175 and 163.8, pour points of -6 °C and -9 °C, flash points of 178 and 104 °C, and low oxidative stability, respectively. Their properties (mainly very high viscosity indices) make them suitable to be used as base stocks in lubricant formulation industries.

Organocatalytic Synthesis and Antitumor Activity of Novel 1,2,3-triazoles Derived from Fatty ß-ketoesters.

BACKGROUND: Developing methods to synthesize highly functionalized and complex 1,2,3- triazoles from various combinations of substrates remains a significant challenge in organic synthesis. Thus, to the best of our knowledge, an organocatalytic approach to synthesize 1,2,3-triazoles derived from fatty acids has not been explored. OBJECTIVE: In this sense, we describe here the organocatalyzed synthesis and preliminary results of antitumor and cytotoxic activity of a range of 1,2,3-triazoles derived from fatty esters. METHODS: To synthesize 1,2,3-triazoles 3 derived from fatty ß-ketoesters, we performed the reaction of appropriate aryl azides 2a-j with ß -ketoesters 1a-c in the presence of 5 mol% of DBU using DMSO as a solvent at 70 °C for 24 h. The viability of 5637 cells was determined by measuring the reduction of soluble MTT to water-insoluble formazan. The IC50 concentration that inhibits 50% of cell growth and the results were obtained by at least three independent experiments in triplicate for each test. RESULTS: Through enolate-mediated organocatalysis, 1,2,3-triazoles 3 derived from fatty ß-ketoesters were synthesized in moderate to excellent yields by reacting fatty esters 1 with aryl azides 2 in the presence of a catalytic amount of 1,8-diazabicyclo[5.4.0]undec-7-ene (5 mol%). All compounds derived from palmitic acetoacetate 1a were evaluated regarding induced cytotoxicity in vitro in a human bladder cancer cell line, and compounds 3a, 3d, 3e, and 3g were shown to be promising alternatives for bladder cancer treatment and presented the lowest inhibitory concentration of IC50. CONCLUSION: We described a synthetic procedure to prepare 1,2,3-triazoles derived from fatty ß - ketoesters by DBU-catalyzed 1,3-dipolar cycloaddition reactions of fatty esters with different aryl azides. Compounds derived from palmitic acetoacetate were screened for antitumor and cytotoxic activity in vitro in human bladder cancer cell lines, and compounds 3a, 3d, 3e, and 3g showed potential to treat bladder cancer.

Isolation of a new flavonoid and waste to wealth recovery of 6-O-Ascorbyl Esters from Seeds of Aegle marmelos (family- Rutaceae).

Aegle marmelos is a plant species native to India. Commercially available food products such as jam, jelly, candy, squash etc. are prepared from ripe fruit pulp of A. marmelos. Ripe fruit processing accounts for 60% of whole fruit mass while 40% remains unutilized and generates waste (hard shell, pomace, fiber and seeds) on a massive scale which do not have high value applications. A new flavone 3,5,7-trihydroxy-2-(4'-hydroxy-3'-isopentyloxyphenyl-4H-chromen-4-one (5) in addition to the known compounds 1-4, has been isolated from seeds of A. marmelos. Also, compound 7-(3'-methylbut-2'-enyloxy)-2H-chromen-2-one (2) has been isolated for the first time from A. marmelos. The structure of compounds 1-5 was determined by spectral analysis (UV, IR, NMR, etc.). Additionally, the non-edible oil obtained from seeds was investigated for waste to wealth recovery of 6-O-ascorbyl esters in high regioselectivity via one step semi-synthetic approach in the presence of ascorbic acid and H2SO4 at ambient temperature.

Critical aggregates concentration of fatty esters present in biodiesel determined by turbidity and fluorescence.

Biodiesel for combustible engine is available as mixture of fossil diesel and fatty esters obtained by transesterification of vegetable oils. The use of biodiesel reduces the amount of SOx, mainly. However, it was already observed that biodiesel has a different behavior in environment in cases of accidental spill and groundwater contamination. It was noticed that the biodegradation of hydrocarbons (cyclic and aliphatic) in the presence of biodiesel are speeded, although the mechanism is still unclear. Considering the chemical structure of fatty esters, it was investigated the formation of aggregates in water solution by fatty esters present in commercial biodiesel. In Brazil, biodiesel is composed by 95% of fossil diesel and 5% of fatty esters mixture. In this work, fatty esters were treated as neutral surfactant, i.e., it was treated as a molecule with polar and non-polar part. Turbidity and fluorescence were used to determine the critical aggregates concentration (CAC). Water solutions containing fatty esters were examined exploiting changes in turbidity and fluorescence intensity of pyrene. Abrupt changes were attributed to aggregates formation, following the same behavior of traditional amphiphilic compounds. It was determined the CAC for ethyl palmitate, ethyl stearate, ethyl oleate, and ethyl linoleate. The values of CAC for fatty esters varied from 1.91 to 4.27 µmol/L, while CAC for the mixture of esters (biodiesel) was 2.01 for methyl esters and 1.19 for ethyl esters, both prepared using soybean oil. The aggregates formation was also determined by fluorescence measurements considering the changes in intensity of peaks I and III of pyrene. Pyrene senses the changes in environment polarity. The values found of CAC by fluorescence for individual ethyl esters varied from 1.85 to 3.21 µmol/L, while mixtures of ethyl esters was 2.23 and 2.07 µmol/L for mixture of methyl esters. The results clearly showed that fatty esters form aggregates and might be responsible for speed degradation of compounds by accommodation of them in inner part of aggregates.

Liquid Crystal Formation from Sunflower Oil: Long Term Stability Studies.

The Brazilian biodiversity offers a multiplicity of raw materials with great potential in cosmetics industry applications. Some vegetable oils and fatty esters increase skin hydration by occlusivity, keeping the skin hydrated and with a shiny appearance. Sunflower (Helianthus annus L.) oil is widely employed in cosmetic emulsions in the form of soaps, creams, moisturizers and skin cleansers due to the presence of polyphenols and its high vitamin E content. Liquid crystals are systems with many applications in both pharmaceutical and cosmetic formulations and are easily detected by microscopy under polarized light due to their birefringence properties. The aim of this research was to develop emulsions from natural sunflower oil for topical uses. Sunflower oil (75.0% w/w) was combined with liquid vaseline (25.0% w/w) employing a natural self-emulsifying base (SEB) derivative. The high temperature of the emulsification process did not influence the antioxidant properties of sunflower oil. Fatty esters were added to cosmetic formulations and extended stability tests were performed to characterize the emulsions. Fatty esters like cetyl palmitate and cetyl ester increase the formation of anisotropic structures. O/W emulsions showed acidic pH values and pseudoplastic behavior. The presence of a lamellar phase was observed after a period of 90 days under different storage conditions.

Synthesis of the Fatty Esters of Solketal and Glycerol-Formal: Biobased Specialty Chemicals.

The caprylic, lauric, palmitic and stearic esters of solketal and glycerol formal were synthesized with high selectivity and in good yields by a solvent-free acid catalyzed procedure. No acetal hydrolysis was observed, notwithstanding the acidic reaction conditions.

Other factors to consider in the formation of chloropropandiol fatty esters in oil processes.

This paper examines the processing steps of extracting palm oil from fresh fruit bunches in a way that may impact on the formation of chloropropandiol fatty esters (3-MCPD esters), particularly during refining. Diacylglycerols (DAGs) do not appear to be a critical factor when crude palm oils are extracted from various qualities of fruit bunches. Highly hydrolysed oils, in spite of the high free fatty acid (FFA) contents, did not show exceptionally high DAGs, and the oils did not display a higher formation of 3-MCPD esters upon heat treatment. However, acidity measured in terms of pH appears to have a strong impact on 3-MCPD ester formation in the crude oil when heated at high temperatures. The differences in the extraction process of crude palm oil from current commercial processes and that from a modified experimental process showed clearly the effect of acidity of the oil on the formation of 3-MCPD esters. This paper concludes that the washing or dilution step in palm oil mills removes the acidity of the vegetative materials and that a well-optimised dilution/washing step in the extraction process will play an important role in reducing formation of 3-MCPD esters in crude palm oil upon further heat processing.

An electron spin resonance study of non-ionic surfactant vesicles (niosomes).

Certain non-ionic surfactants form lamellar vesicles called niosomes. Being elastic and deformable, niosomes have been used as an efficient vehicle for transdermal drug delivery. However, dynamic properties of niosomes have not been studied extensively. In this study we used electron spin resonance (ESR) technique to measure the membrane fluidity of niosomes. In parallel with phospholipid liposomes, the ESR spectra of 5- and 16-doxyl stearate in niosomes of sorbitan monostearate (Span 60) and sorbitan monooleate (Span 80) showed that motion of the spin label was more restricted at the region near the headgroup than near the bilayer center. Cholesterol increased fluidity of Span 60 niosomes whereas it decreased fluidity of Span 80 niosomes. Dicetyl phosphate added at 10 mol% concentration as a stabilizer had a minimal effect on the membrane fluidity throughout the bilayer. We also used ESR technique to monitor the hydration-induced transformation of Span 60 proniosome gel to niosome and showed that the niosome prepared by hydration of proniosome gel was identical to the niosome obtained from a thin film hydration method. Finally the ESR spectra of Span niosomes were compared with those of polysorbate (Tween) niosomes and polyethoxy fatty ether (Brij) niosomes. Tween niosomes had a bulky headgroup and were much less rigid than Span niosomes. This effect of headgroup size on fluidity was also manifest in Brij niosomes where fluidity increased with the number of ethoxy units in the polyethoxy headgroup.

Microbial degradation of palm (Elaeis guineensis )biodiesel

The kinetics of biodegradation of palm-derived fatty methyl and ethyl esters (Elaeis guineensis biodiesel) by a wild-type aerobic bacterial population was measured at 20 °C, as the rate of oxygen uptake by a manometric technique. The methyl and ethyl biodiesels were obtained by potassium-hydroxide catalysed transesterification of palm oil, respectively. The bacterial flora included the genera Bacillus, Proteus, Pseudomonas, Citrobacter and Enterobacter. The rate of oxygen uptake for palm biodiesel is similar to the quantity observed in the biodegradation of 1.0 mM solutions of simple substrates such as carbohydrates or amino acids.Palm methyl or ethyl biodiesel is subjected to facile aerobic biodegradation by wild-type bacteria commonly present in natural open environments. This result should lessen any environmental concern for its use as alternative fuel, solvent or lubricant.

La cinética de la biodegradación de los ésteres metílicos y etílicos derivados de palma (biodiesel) por una población silvestre de bacterias aeróbicas fue medida a 20 °C, como medición manométrica del consumo de oxígeno. Los ésteres metílicos y etílicos se obtuvieron por transesterificación del aceite de palma con metanol y etanol,respectivamente. La flora bacteriana incluyó a los géneros Bacillus, Proteus, Pseudomonas, Citrobacter y Enterobacter. Las velocidades de consumo de oxígeno para las muestras de biodiesel fueron similares a lo observado en la biodegradación de disoluciones 1.0 mM de sustratos sencillos solubles en agua, tales como carbohidratos, aminoácidos y albúmina de huevo.