Toxicity of allyl esters in insect cell lines and in Spodoptera littoralis larvae

We investigated the effects of five allyl esters, two aromatic (allyl cinnamate and allyl 2-furoate) and three aliphatic (allyl hexanoate, allyl heptanoate, and allyl octanoate) in established insect cell lines derived from different species and tissues. We studied embryonic cells of the fruit fly Drosophila melanogaster (S2) (Diptera) and the beet armyworm Spodoptera exigua (Se4) (Lepidoptera), fat body cells of the Colorado potato beetle Leptinotarsa decemlineata (CPB) (Coleoptera), ovarian cells of the silkmoth Bombyx mori (Bm5), and midgut cells of the spruce budworm Choristoneura fumiferana (CF203) (Lepidoptera). Cytotoxicity was determined with use of MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] and trypan blue. In addition, we tested the entomotoxic action of allyl cinnamate against the cotton leafworm Spodoptera littoralis .The median (50%) cytotoxic concentrations (EC50s) of the five allyl esters in the MTT bioassays ranged between 0.25 and 27 mM with significant differences among allyl esters (P = 0.0012), cell lines (P < 0.0001), and the allyl estercell line interaction (P < 0.0001). Allyl cinnamate was the most active product, and CF203 the most sensitive cell line. In the trypan blue bioassays, cytotoxicity was produced rapidly and followed the same trend observed in the MTT bioassay. In first instars of S. littoralis, allyl cinnamate killed all larvae at 0.25% in the diet after 1 day, while this happened in third instars after 5 days. The LC50 in first instars was 0.08%. In addition, larval weight gain was reduced (P < 0.05) after 1 day of feeding on diet with 0.05%. In conclusion, the data provide evidence of the significant but differential cytotoxicity among allyl esters in insect cells of different species and tissues. Midgut cells show high sensitivity, indicating the insect midgut as a primary target tissue. Allyl cinnamate caused rapid toxic effects in S. littoralis larvae at low concentrations, suggesting further potential for use in pest control.

Application of 1-Allyl-3-(1-butyl)imidazolium Chloride in the Synthesis of Cellulose Esters: Properties of the Ionic Liquid, and Comparison with Other Solvents

The ionic liquid (IL), 1-allyl-3-(1-butyl)imidazolium chloride (AlBuImCl), has been synthesized and its properties determined. Increase in the temperature increased its conductivity and decreased its density, polarity, and viscosity. Microcrystalline cellulose (MCC), dissolves in thisIL by heating at 80 degrees C; this did not affect its degree of polymerization, decreased its index of crystallinity (Ic), and changed in morphology after regeneration. Convenient acylation of MCC was achieved by using 50% excess anhydride at 80 degrees C, for 24 or 48 h for acetic and butyric anhydride, respectively. The composition of the mixed esters depended on the initial ratio of the anhydrides, and their order of addition.

Trypanosoma cruzi: inhibition of alpha-hydroxyacid dehydrogenase isozyme II by N-allyl and N-propyl oxamates and their effects on intact epimastigotes

N-allyl (NAOx) and N-propyl (NPOx) oxamates were designed as inhibitors of alpha-hydroxyacid dehydrogenase (HADH) isozyme II from Trypanosoma cruzi. The kinetic studies showed that NAOx and NPOx were competitive inhibitors of HADH-isozyme II (Ki = 72 µM, IC50 = 0.33 mM and 70 µM, IC50 = 0.32 mM, respectively). The attachment of the allylic and propylic chains to nitrogen of the competitive inhibitor oxamate (Ki = 0.91 mM, IC50 = 4.25 mM), increased 12.6 and 13-folds respectively, the affinity for T. cruzi HADH-isozyme II. NAOx and NPOx were selective inhibitors of HADH-isozyme II, because other T. cruzi dehydrogenases were not inhibited by these substances. Since HADH-isozyme II participates in the energy metabolism of T. cruzi, a trypanocidal effect can be expected with these inhibitors. However, we were not able to detect any trypanocidal activity with these oxamates. When the corresponding ethyl esters of N-allyl (Et-NAOx) and N-propyl (Et-NPOx) oxamates were tested as a possible trypanocidal prodrugs, in comparison with nifurtimox and benznidazole, the expected trypanocidal effects were obtained.

Microwave-Assisted Derivatization of Cellulose in an Ionic Liquid: An Efficient, Expedient Synthesis of Simple and Mixed Carboxylic Esters

Microwave (MW)-assisted cellulose dissolution in ionic liquids (ILs) has routinely led either to incomplete biopolymer solubilization, or its degradation. We show that these problems can be avoided by use of low-energy MW heating, coupled with efficient stirring. Dissolution of microcrystalline cellulose in the IL 1-allyl-3-methylimidazolium chloride has been achieved without changing its degree of polymerization; regenerated cellulose showed pronounced changes in its index of crystallinity, surface area, and morphology. MW-assisted functionalization of MCC by ethanoic, propanoic, butanoic, pentanoic, and hexanoic anhydrides has been studied. Compared with conventional heating, MW irradiation has resulted in considerable decrease in dissolution and reaction times. The value of the degree of substitution (DS) was found to be DS(ethanoate) > DS(propanoate) > DS(butanoate). The values of DS(pentanoate) and DS(hexanoate) were found to be slightly higher than DS(ethanoate). This surprising dependence on the chain length of the acylating agent has been reported before, but not rationalized. On the basis of the rate constants and activation parameters of the hydrolysis of ethanoic, butanoic, and hexanoic anhydrides in aqueous acetonitrile (a model acyl transfer reaction), we suggest that this result may be attributed to the balance between two opposing effects, namely, steric crowding and (cooperative) hydrophobic interactions between the anhydride and the cellulosic surface, whose lipophilicity has increased, due to its partial acylation. Four ethanoate-based mixed esters were synthesized by the reaction with a mixture of the two anhydrides; the ethanoate moiety predominated in all products. The DS is reproducible and the IL is easily recycled. (C) 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 134-143, 2010

Synthesis, screening for antiacetylcholinesterase activity and binding mode prediction of a new series of [3-(disubstituted-phosphate)-4,4,4-trifluoro-butyl]-carbamic acid ethyl esters

A series of nine new [3-(disubstituted-phosphate)-4,4,4-trifluoro-butyl]-carbamic acid ethyl esters (phosphate-carbamate compounds) was obtained through the reaction of (4,4,4-trifluoro-3-hydroxybut-1-yl)-carbamic acid ethyl esters with phosphorus oxychloride followed by the addition of alcohols. The products were characterized by ¹H, 13C, 31P, and 19F NMR spectroscopy, GC-MS, and elemental analysis. All the synthesized compounds were screened for acetylcholinesterase (AChE) inhibitory activity using the Ellman method. All compounds containing phosphate and carbamate pharmacophores in their structures showed enzyme inhibition, being the compound bearing the diethoxy phosphate group (2b) the most active compound. Molecular modeling studies were performed to investigate the detailed interactions between AChE active site and small-molecule inhibitor candidates, providing valuable structural insights into AChE inhibition.

Clean preparation of methyl esters in one-step oxidative esterification of primary alcohols catalyzed by supported gold nanoparticles

Methyl esters were prepared by the clean, one-step catalytic esterification of primary alcohols using molecular oxygen as a green oxidant and a newly developed SiO(2)-supported gold nanoparticle catalyst. The catalyst was highly active and selective in a broad range of pressure and temperature. At 3 atm O(2) and 130 degrees C benzyl alcohol was converted to methyl benzoate with 100% conversion and 100% selectivity in 4 h of reaction. This catalytic process is much ""greener"" than the conventional reaction routes because it avoids the use of stoichiometric environmentally unfriendly oxidants, usually required for alcohol oxidation, and the use of strong acids or excess of reactants or constant removal of products required to shift the equilibrium to the desired esterification product.

Determination of eight fatty acid ethyl esters in meconium samples by headspace solid-phase microextraction and gas chromatography-mass spectrometry

A number of fatty acid ethyl esters (FAEEs) have recently been detected in meconium samples. Several of these FAEEs have been evaluated as possible biomarkers for in utero ethanol exposure. In the present study, a method was optimized and validated for the simultaneous determination of eight FAEEs (ethyl laurate, ethyl myristate, ethyl palmitate, ethyl palmitoleate, ethyl stearate, ethyl oleate, ethyl linoleate and ethyl arachidonate) in meconium samples. FAEEs were extracted by headspace solid-phase microextraction. Analyte detection and quantification were carried out using GC-MS operated in chemical ionization mode. The corresponding D5-ethyl esters were synthesized and used as internal standards. The LOQ and LOD for each analyte were <150 and <100 ng/g, respectively. The method showed good linearity (r(2)>0.98) in the concentration range studied (LOQ -2000 ng/g). The intra- and interday imprecision, given by the RSD of the method, was lower than 15% for all FAEEs studied. The validated method was applied to 63 authentic specimens. FAEEs could be detected in alcohol-exposed newborns ( >600 ng/g cumulative concentration). Interestingly, FAEEs could also be detected in some non-exposed newborns, although the concentrations were much lower than those measured in exposed cases.

QSAR Modeling of a Set of Pyrazinoate Esters as Antituberculosis Prodrugs

Tuberculosis is an infection caused mainly by Mycobacterium tuberculosis. A first-line antimycobacterial drug is pyrazinamide (PZA), which acts partially as a prodrug activated by a pyrazinamidase releasing the active agent, pyrazinoic acid (POA). As pyrazinoic acid presents some difficulty to cross the mycobacterial cell wall, and also the pyrazinamide-resistant strains do not express the pyrazinamidase, a set of pyrazinoic acid esters have been evaluated as antimycobacterial agents. In this work, a QSAR approach was applied to a set of forty-three pyrazinoates against M. tuberculosis ATCC 27294, using genetic algorithm function and partial least squares regression (WOLF 5.5 program). The independent variables selected were the Balaban index (I), calculated n-octanol/water partition coefficient (ClogP), van-der-Waals surface area, dipole moment, and stretching-energy contribution. The final QSAR model (N = 32, r(2) = 0.68, q(2) = 0.59, LOF = 0.25, and LSE = 0.19) was fully validated employing leave-N-out cross-validation and y-scrambling techniques. The test set (N = 11) presented an external prediction power of 73%. In conclusion, the QSAR model generated can be used as a valuable tool to optimize the activity of future pyrazinoic acid esters in the designing of new antituberculosis agents.

A new synthesis of chiral aminoalkyloxazolecarboxylate esters from isoxazol-5(2H)-ones: the synthesis of almazoles A and B

2-(1-Aminoalkyl)oxazole-4 and 5-carboxylates are available, without detectable racemisation, by a sequence involving N-acylation of isoxazol-5(2H)one carboxylates with phthalimidoamino acids, photolysis of the acylated product, and hydrazinolysis. An application of the procedure to the synthesis of almazole A and B is described (C) 1998 Elsevier Science Ltd. All rights reserved.

Topical penetration of commercial salicylate esters and salts using human isolated skin and clinical microdialysis studies

Aims The penetration of active ingredients from topically applied anti-inflammatory pharmaceutical products into tissues below the skin is the basis of their therapeutic efficacy. There is still controversy as to whether these agents are capable of direct penetration by diffusion through the tissues or whether redistribution in the systemic circulation is responsible for their tissue deposition below the application site. Methods The extent of direct penetration of salicylate from commercial ester and salt formulations into the dermal and subcutaneous tissue of human volunteers was determined using the technique of cutaneous microdialysis. We also examined differences in the extent of hydrolysis of the methylester of salicylate applied topically in human volunteers and in vitro skin diffusion cells using full-thickness skin and epidermal membranes. Results The present study showed that whilst significant levels of salicylate could be detected in the dermis and subcutaneous tissue of volunteers treated with the methylsalicylate formulation, negligible levels of salicylate were seen following application of the triethanolamine salicylate formulation. The tissue levels of salicylate from the methylsalicylate formulation were approx. 30-fold higher than the plasma concentrations. Conclusion The absorption and tissue concentration profiles for the commercial methylsalicylate formulation are indicative of direct tissue penetration and not solely redistribution by the systemic blood supply.

Hepatic disposition and metabolite kinetics of a homologous series of diflunisal esters

The hepatic disposition and metabolite kinetics of a homologous series of diflunisal O-acyl esters (acetyl, butanoyl, pentanoyl, anti hexanoyl) were determined using a single-pass perfused in situ rat liver preparation. The experiments were conducted using 2% BSA Krebs-Henseleit buffer (pH 7.4), and perfusions were performed at 30 mL/min in each liver. O-Acyl esters of diflunisal and pregenerated diflunisal were injected separately into the portal vein. The venous outflow samples containing the esters and metabolite diflunisal were analyzed by high performance liquid chromatography (HPLC). The normalized outflow concentration-time profiles for each parent ester and the formed metabolite, diflunisal, were analyzed using statistical moments analysis and the two-compartment dispersion model. Data (presented as mean +/- standard error for triplicate experiments) was compared using ANOVA repeated measures, significance level P < 0.05. The hepatic availability (AUC'), the fraction of the injected dose recovered in the outflowing perfusate, for O-acetyldiflunisal (C2D = 0.21 +/- 0.03) was significantly lower than the other esters (0.34-0.38). However, R-N/f(u), the removal efficiency number R-N divided by the unbound fraction in perfusate f(u), which represents the removal efficiency of unbound ester by the liver, was significantly higher for the most lipophilic ester (O-hexanoyldiflunisal, C6D = 16.50 +/- 0.22) compared to the other members of the series (9.57 to 11.17). The most lipophilic ester, C6D, had the largest permeability surface area (PS) product (94.52 +/- 38.20 mt min-l g-l liver) and tissue distribution value VT (35.62 +/- 11.33 mL g(-1) liver) in this series. The MTT of these O-acyl esters of diflunisal were not significantly different from one another. However, the metabolite diflunisal MTTs tended to increase with the increase in the parent ester lipophilicity (11.41 +/- 2.19 s for C2D to 38.63 +/- 9.81 s for C6D). The two-compartment dispersion model equations adequately described the outflow profiles for the parent esters and the metabolite diflunisal formed from the O-acyl esters of diflunisal in the liver.

Adsorption of flavour esters on granular activated carbon

This article reports on the liquid phase adsorption of flavour esters onto granular activated carbon. Ethyl propionate, ethyl butyrate, and ethyl isovalerate were used as adsorbates, and Filtrasorb 400 activated carbon was chosen as the adsorbent. Sips, Toth, Unilan, and Dubinin-Radushkevich isotherm equations which are generally used for heterogeneous adsorbents were used to fit the data. Although satisfactory in fitting the data, inconsistency in parameter values indicated these models to be inadequate. On the other hand the Dubinin-Radushkevich model gave more consistent and meaningful parameter values and adsorption capacities. By employing the Dubinin-Radushkevich equation, the limiting volume of the adsorbed space, which equals the accessible micropore volume, was determined, and found to correlate with the value from carbon dioxide adsorption.

Free radical copolymerization of methyl methacrylate and allyl acetate Part 2 structure and properties

The structure of the product from the free radical bulk copolymerization of methyl methacrylate (MMA) and allyl acetate (AAc) was investigated. The mole fraction of AAc plays an important role in the copolymerization of these two monomers. Molecular weight (MW) and molecular weight distribution (MWD) are completely altered when the feed composition is dominantly AAc. NMR spectroscopy confirmed the incorporation of AAc into the polymer. However, no allyl-allyl linkages were observed at low conversions. T-g was found to be affected by the incorporation of AAc into the polymer. (C) 2001 Society of Chemical Industry.

Copolymerization of methyl methacrylate and allyl acetate Part I. Rate of reaction

Free radical bulk copolymerization of methyl methacrylate (MMA) and allyl acetate (AAc) has been investigated using electron spin resonance (ESR) and FT-near infrared (FTNIR) spectroscopy. Data are used to evaluate the rate constants. The mole fraction of AAc plays an important role in the copolymerization of these two monomers. AAc not only delays the Trommsdorff effect but also increases the onset of percentage total conversion at which the Trommsdorff region begins. With AAc fraction 0.5 and higher, no Trommsdorff effect was observed. Inclusion of AAc into copolymer structure mainly occurs in the Trommsdorf region or when the AAc fraction in the comonomer feed is dominant. This is associated with a drop in the concentration of propagating radicals. However, ESR spectra indicate that the MMA propagating radical is predominant during the reaction. In the comonomer mixtures where a Trommsdorff region can be observed, the addition of AAc does not produce any significant change in k(p) and k(t) in the steady state region. Major changes in k(p) and k(t) are observed after the gel point and glassy state, respectively. (C) 2001 Society of Chemical Industry.

Solubility of selected esters in supercritical carbon dioxide

The solubility of ethyl propionate, ethyl butyrate, and ethyl isovalerate in supercritical carbon dioxide was measured at temperature ranging from 308.15 to 333.15 K and pressure ranging from 85 to 195 bar. At the same temperature, the solubility of these compounds increases with pressure. The crossover pressure region was also observed in this study. The experimental data were correlated by the semi-empirical Chrastil equation and Peng-Robinson equation of state (EOS) using several mixing rules. The Peng-Robinson EOS gives better solubility prediction than the empirical Chrastil equation. (C) 2002 Elsevier Science B.V. All rights reserved.