Alkyl Gallates Research Articles

Effects of alkyl gallates, fatty acids, and acylglycerols on the growth of the psychrotolerant bacterium Sporosarcina sp. S92h

Abstract Sporosarcina species are psychrotolerant endospore-forming bacteria that are predominantly isolated from processed minced fish meat (surimi). Their levels should be controlled to maintain the quality of surimi-based food products. Our previous study suggested that the fatty acid composition of the cell membrane is an important factor for the growth of Sporosarcina species under cold conditions. In this study, we examined the effects of alkyl gallates, fatty acids, and acylglycerols on the growth of Sporosarcina sp. S92h in TSB medium at 10 °C and 30 °C. The results illustrated that the alkyl gallates isoamyl gallate, octyl gallate, and lauryl gallate; the fatty acids oleic acid, linoleic acid, and α-linolenic acid; and the acylglycerol monolaurin inhibited the growth of Sporosarcina sp. S92h for 10 days at 10 °C at a concentration of 0.2 mM. We found that compounds that exerted significant growth-inhibitory effects have similar molecular weights (range, 240.3–338.4) and ACD/LogP values (range, 3.48–7.70). These data will be useful for exploring more effective compounds to inhibit the growth of Sporosarcina species and contribute to quality control for surimi-based foods.

Purification and characterization of FtsZ from the citrus canker pathogen Xanthomonas citri subsp. citri.

Xanthomonas citri subsp. citri (Xac) is the causative agent of citrus canker, a plant disease that significantly impacts citriculture. In earlier work, we showed that alkylated derivatives of gallic acid have antibacterial action against Xac and target both the cell division protein FtsZ and membrane integrity in Bacillus subtilis. Here, we have purified native XacFtsZ and characterized its GTP hydrolysis and polymerization properties. In a surprising manner, inhibition of XacFtsZ activity by alkyl gallates is not as strong as observed earlier with B. subtilis FtsZ. As the alkyl gallates efficiently permeabilize Xac membranes, we propose that this is the primary mode of antibacterial action of these compounds.

Trapping of glyoxal by propyl, octyl and dodecyl gallates and their mono-glyoxal adducts

Glyoxal (GO) is one of the major toxic intermediates generated during lipid oxidation and degradation. We investigated the inhibitory activities and mechanisms of propyl, octyl, and dodecyl gallates (PG, OG, and DG) on the formation of GO in buffer and during thermo-processing of corn oil, and the anti-carbonyl and antioxidative activities of the mono-GO adducts of PG, OG, and DG. Our results suggested that alkyl gallates could more effectively trap GO than gallic acid. The major mono-GO adducts of PG, OG, and DG were purified and their structures were elucidated based on their 1H, 13C, 2D-NMR, and HRMS data. We further demonstrated that the mono-GO (MG) adducts retained the anti-carbonyl and antioxidative activities. This is the first study to demonstrate that alkyl gallates, the popular food additives, could prevent not only food oxidation, but also the formation of toxic reactive carbonyl species and their corresponding advanced glycation end products (AGEs) during food processing.

Antibacterial activity of monoacetylated alkyl gallates against Xanthomonas citri subsp. citri.

Asiatic citrus canker (ACC) is an incurable disease of citrus plants caused by the Gram-negative bacterium Xanthomonas citri subsp. citri (X. citri). It affects all the commercially important citrus varieties in the major orange producing areas around the world. Control of the pathogen requires recurrent sprays of copper formulations that accumulate in soil and water reservoirs. Here, we describe the improvement of the alkyl gallates, which are potent anti-X. citri compounds, intended to be used as alternatives to copper in the control of ACC. Acetylation of alkyl gallates increased their lipophilicity, which resulted in potentiation of the antibacterial activity. X. citri exposed to the acetylated compounds exhibited increased cell length that is consistent with the disruption of the cell division apparatus. Finally, we show that inhibition of cell division is an indirect effect that seemed to be caused by membrane permeabilization, which is apparently the primary target of the acetylated alkyl gallates.

Salt-dependent elution of uncharged aromatic solutes in ion-exchange chromatography

Ion-exchange chromatography and multimodal ion-exchange chromatography are widely used for the separation of small molecules, peptides and proteins. Salts generally attenuate the electrostatic interactions between charged moieties of solutes and those of resins through electrostatic screening. However, little is known about how salts affect the interaction between the uncharged moieties of the solutes, such as aromatic moieties, and the charged moieties of the resins. In this study, we used alkyl gallates as model aromatic solutes to investigate the interaction mechanism of aromatic moieties with multimodal and conventional ion-exchange resins. Interestingly, alkyl gallates retained by these resins were readily eluted from the columns by the addition of 0.01–1 M NaCl, even though the alkyl gallates used contained no charged group. Molecular dynamics (MD) simulations were performed to understand the mechanism of these interactions. The MD simulation with a conventional force field showed that 1 M NaCl enhances the binding of an alkyl gallate molecule to the ligand, which contradicts the experimental results. Thus, we modified the force field to express a cation–π interaction between sodium ions and aromatic moieties, which successfully reproduced the experimental results at 1 M, suggesting that the cation–π interaction between sodium ions and aromatic moieties plays a crucial role in reducing the binding affinity of alkyl gallates for the ligands. These results provide new information indicating that aromatic moieties, including the aromatic residues of proteins and nucleobases of nucleic acids, favorably interact with multimodal and conventional ion-exchange resins and that cations, such as sodium ions, contribute to attenuating the binding of aromatic moieties to the ligands.

Enhancement of the antioxidant efficiency of gallic acid derivatives in intact fish oil-in-water emulsions through optimization of their interfacial concentrations.

The antioxidant (AO) efficiencies and the distributions of gallic acid (GA) and a series of alkyl gallates (propyl, PG, butyl, BG, octyl, OG and lauryl, LG) were determined in intact fish oil-in-water emulsions. The efficiency of the AOs in inhibiting the oxidation of the fish oil lipids increases upon increasing AO hydrophobicity up to a maximum (∼3-fold) at the octyl derivative, after which the efficiency decreases (LG). The observed non-linear variation in the efficiency with the AO alkyl chain length parallels those of the percentages of AOs in the interfacial region and of their interfacial concentrations, but does not parallel that of the percentage of AOs in the oil region. The interfacial AO concentrations are 20-100 times greater than the stoichiometric (added) antioxidant concentration, depending on the interfacial surfactant volume fraction ΦI, meanwhile the AO concentrations in the oil are similar or slightly higher (1-6 fold) and the concentrations in the aqueous region are much smaller (0.8-10 fold). The effects of the oil to water (o : w) ratio on the interfacial concentrations are complex and depend on both the hydrophobicity of the AO and ΦI. An increase in the o : w ratio favors incorporation of hydrophilic AOs to the interfacial region of emulsions but it decreases the incorporation of hydrophobic AOs. Results provide, for the first time, experimental evidence supporting the interfacial region of emulsions as the main site of production of lipid radicals. Results also provide physical evidence that the efficiency of AOs depends on their interfacial concentrations, which can be modulated by increasing the hydrophobicity of the AOs and by employing the minimum amount of surfactant necessary to stabilize the emulsions. Changes in the o : w ratio can also be used to modulate the interfacial concentrations of hydrophobic (OG, LG, and to a lesser extent BG) or hydrophilic (GA) AOs, but not those of AOs of intermediate hydrophobicity (PG).

Nanoparticulate delivery systems for alkyl gallates: Influence of the elaboration process on particle characteristics, drug encapsulation and in-vitro release

PLA nanoparticles loaded with n-alkyl gallates (AGs) were prepared either by nanoprecipitation (NP) or by O/W emulsion/solvent evaporation (E/SE). A nonionic hydrophobically modified polysaccharide was used for surface coverage and for ensuring colloidal stability. Different parameters were systematically assessed to enhance the drug incorporation, with the aim of obtaining monomodal and narrow particle size distributions. The nanoparticles were characterized by 1H NMR, transmission electron microscopy (TEM) and laser light scattering granulometry. The colloidal stability of suspensions was evaluated after incubation in NaCl solutions and was maintained up to 1M NaCl. The mean particle diameter and the width of size distribution were found very similar for both processes (slightly lower diameters when using E/SE) with various drug loadings. The amount of encapsulated AG by E/SE was about twice that encapsulated by NP. The in-vitro release of AG was evaluated under sink conditions and no burst effect was observed. Release curves were successfully modeled using the Fick diffusion model with a constant diffusion coefficient and assuming non-swellable particles. Diffusion coefficients of AG loaded in nanoparticles prepared by NP were higher than those found in nanoparticles elaborated by E/SE.

Ethyl Gallate Displays Elicitor Activities in Tobacco Plants.

Alkyl gallates showed elicitor activities on tobacco in both whole plants and cell suspensions. Methyl gallate (MG), ethyl gallate (EG), and propyl gallate (PG) infiltration into tobacco leaves induced hypersensitive reaction-like lesions and topical production of autofluorescent compounds revealed under UV light. When sprayed on tobacco plants at 5 mM, EG promoted upregulation of defense-related genes such as the antimicrobial PR1, β-1,3-glucanase PR2, Chitinase PR3, and osmotin PR5 target genes. Tobacco BY-2 cells challenged with EG underwent cell death in 48 h, which was significantly reduced in the presence of the protease inhibitor aprotinin. The three alkyl gallates all caused alkalinization of the BY-2 extracellular medium, whereas gallic acid did not trigger any pH variation. Using EGTA or LaCl3, we showed that Ca2+ mobilization occurred in BY-2 cells elicited with EG. Overall, our findings are the first evidence of alkyl gallate elicitor properties with early perception events on the plasma membrane, potential hypersensitive reactions, and PR-related downstream defense responses in tobacco.

Derivatives of alkyl gallate triphenylphosphonium exhibit antitumor activity in a syngeneic murine model of mammary adenocarcinoma

We previously demonstrated that alkyl gallates coupled to triphenylphosphine have a selective and efficient antiproliferative effect by inducing mitochondrial uncoupling in vitro due to the increased mitochondrial transmembrane potential of tumor cells. Therefore, in this work, the in vivo antitumor activities of alkyl gallate triphenylphosphonium derivatives (TPP+C8, TPP+C10 and TPP+C12) were evaluated in a syngeneic murine model of breast cancer. We found that TPP+C10 increased the cytosolic ADP/ATP ratio and significantly increased the AMP levels in a concentration-dependent manner in TA3/Ha murine mammary adenocarcinoma cells. Interestingly, TPP+C10 induced a decrease in the levels of cellular proliferation markers and promoted caspase-3 activation in tumor-bearing mice. Additionally, TPP+C10 inhibited tumor growth in the syngeneic mouse model. Importantly, 30days of intraperitoneal (i.p.) administration of the combination of TPP+C10 (10mg/kg/48h) and the antibiotic doxycycline (10mg/kg/24h) completely eliminated the subcutaneous tumor burden in mice (n=6), without any relapses at 60days post-treatment. This enhancement of the individual activities of TPP+C10 and doxycycline is due to the uncoupling of oxidative phosphorylation by TPP+C10 and the inhibition of mitochondrial biogenesis by doxycycline, as demonstrated by loss of mitochondrial mass and overexpression of PGC1-α as an adaptive response. Moreover, i.p. administration of TPP+C10 (10mg/kg/24h) to healthy mice did not produce toxicity or damage in organs important for drug metabolism and excretion, as indicated by hematological, biochemical and histological assessments. These findings suggest that the combination of TPP+C10 with doxycycline is a valuable candidate therapy for breast cancer management.

Evaluation of cytotoxic, apoptotic, mutagenic, and chemopreventive activities of semi-synthetic esters of gallic acid

Gallic acid and its derivatives are phenolic compounds widely used as food supplements in the form of capsules, liquid extracts, and ointments owing to their good antioxidant properties. Besides, these compounds are potent inhibitors of fungi, bacteria, and some viruses and possess strong antiproliferative and chemopreventive activities. However, gallic acid derivatives are also known to exert harmful effects like mutagenicity and cytotoxicity. The present study aimed to understand and explore the toxicological risks of these compounds. For this, a series of alkyl gallates with side chains varying from five to eight carbons (pentyl, hexyl, heptyl, and octyl gallates) were evaluated for their cytotoxic and pro-apoptotic potential. In addition, the genotoxic effects of alkyl gallates were measured in HepG2 cells using the single cell gel electrophoresis (SCGE)/comet assay and the cytokinesis-blocked micronucleus (CBMN) test. In both the tests, the substances did not induce any significant differences when compared to the control group. In addition, alkyl gallates exhibited a chemopreventive effect, thereby considerably reducing the mutagenicity caused by H2O2. In conclusion, our results suggest that alkyl gallates are non-genotoxic, non-mutagenic, and pro-apoptotic agents, which may serve as suitable and promising candidates for preventing chemically-induced chromosomal damage.

A characterization of the antimalarial activity of the bark of Cylicodiscus gabunensis Harms

Ethnopharmacological relevance and aimA decoction of the bark of Cylicodiscus gabunensis Harms is used as a traditional medicine in the treatment of malaria in Nigeria. This study aims to validate the antimalarial potency of this decoction in vitro against Plasmodium falciparum and define potential bioactive constituents within the C. gabunensis bark. Materials and methodsA bioassay-guided separation and fractionation protocol was applied to C. gabunensis extracts, exploiting the use of a Malaria Sybr Green I Fluorescence assay method to monitor antiproliferative effects on parasites as well as define 50% inhibition concentrations. Spectroscopic techniques, including GC-MS, TOF LC-MS and 1H NMR were used to identify phytochemicals present in bioactive fractions. Analogues of gallic acid were synthesized de novo to support the demonstration of the antimalarial action of phenolic acids identified in C. gabunensis bark. In vitro cytotoxicity of plant extracts, fractions and gallate analogues was evaluated against the HepG2 cell line. ResultsThe antimalarial activity of ethanolic extracts of C. gabunensis bark was confirmed in vitro, with evidence for phenolic acids, primarily gallic acid and close analogues such as ethyl gallate, likely providing this effect. Further fractionation produced the most potent fraction with a 50% inhibitory concentration of 4.7µg/ml. Spectroscopic analysis, including 1H NMR, LC-MS and GC-MS analysis of this fraction and its acid hydrolyzed products, indicated the presence of conjugates of gallic acid with oligosaccharides. The extracts/fractions and synthetic alkyl and alkenyl gallates showed moderate selectivity against P. falciparum. ConclusionsThese results support the use of the bark of C. gabunensis as a traditional medicine in the treatment of human malaria, with phenolic acid oligosaccharide complexes evident in the most bioactive fractions.

Inhibitory Activities of Alkyl Syringates and Related Compounds on Aflatoxin Production.

Inhibitors of aflatoxin production of aflatoxigenic fungi are useful for preventing aflatoxin contamination in crops. As methyl syringate weakly inhibits aflatoxin production, aflatoxin production inhibitory activities of additional alkyl syringates with alkyl chains from ethyl to octyl were examined. Inhibitory activity toward aflatoxin production of Aspergillus flavus became stronger as the length of the alkyl chains on the esters became longer. Pentyl, hexyl, heptyl, and octyl syringates showed strong activity at 0.05 mM. Heptyl and octyl parabens, and octyl gallate also inhibited aflatoxin production as strongly as octyl syringate. Alkyl parabens and alkyl gallates inhibit the complex II activity of the mitochondrial respiration chain; thus, whether alkyl syringates inhibit complex II activity was examined. Inhibitory activities of alkyl syringates toward complex II also became stronger as the length of the alkyl chains increased. The complex II inhibitory activity of octyl syringate was comparable to that of octyl paraben and octyl gallate. These results suggest that alkyl syringates, alkyl parabens, and alkyl gallates, including commonly used food additives, are useful for aflatoxin control.

Foams Stabilized by In-Situ Surface-Activated Nanoparticles in Bulk and Porous Media

Summary Foams for subsurface applications are traditionally stabilized by surfactants. The goal of this work is to study foam stabilization by nanoparticles—in particular, by in-situ surface-hydrophobization of hydrophilic nanoparticles. The interfacial properties of the nanoparticles were modulated by the attachment of short-chain surface modifiers (alkyl gallates) that render them partially hydrophobic, but still fully dispersible in water. First, static foams were generated with nanoparticles with varying concentrations of surface modifiers. The decay of foam height with time was measured, and half-lives were determined. Optical micrographs of foam stabilized by surface-modified nanoparticles (SMNPs) and surfactant were recorded. Second, aqueous foams were created in-situ by coinjecting the SMNP solutions with nitrogen gas through a Berea sandstone core at a fixed quality. Pressure drop across the core was measured to estimate the achieved resistance factor. These pressure-drop results were then compared with those of a typical surfactant (alpha olefin sulfonate, alkyl polyglucoside) under similar conditions. Finally, oil-displacement experiments were conducted in Berea cores with surfactant and SMNP solutions as foaming agents (coinjection with nitrogen gas). A Bartsch shake test revealed the strong foaming tendency of SMNPs even with a very low initial surface-modifier concentration (0.05 wt%), whereas hydrophilic nanoparticles alone could not stabilize foam. The bubble texture of foam stabilized by SMNPs was finer than that with surfactants, indicating a stronger foam. As the degree of surface coating increased, the resistance factor of SMNP foam in a Berea core increased significantly. The corefloods in the sandstone cores with a reservoir crude oil showed that immiscible foams with SMNP solution can recover a significant amount of oil (20.6% of original oil in place) over waterfloods.

Novel adjuvant strategy to potentiate bacitracin against MDR MRSA.

Bacitracin is an antimicrobial peptide that is frequently used as an active ingredient in antimicrobial ointments. However, bacitracin resistance is highly prevalent in community-associated MRSA (CA-MRSA) strains and significantly compromises the effectiveness of existing antimicrobial ointments. In this study, we aimed to develop novel adjuvants to enhance the antimicrobial activity of bacitracin by using alkyl gallates. The growth of MRSA USA300, the predominant CA-MRSA strain in the USA, was determined in the presence of bacitracin and alkyl gallates at various concentrations. The viability of USA300 and MDR clinical isolates of MRSA was measured after exposure to various combinations of bacitracin and alkyl gallates. Whereas 100 U/mL bacitracin did not inhibit USA300, 1 U/mL bacitracin in combination with as low as 2 mg/L octyl gallate (OG) and 8 mg/L dodecyl gallate (DG), respectively, completely inhibited the growth of USA300. Among the tested alkyl gallates, OG most significantly enhanced the bactericidal activity of bacitracin. For example, 10(-3) U/mL bacitracin with 5 mg/L OG effectively killed USA300, which is an ∼200 000-fold decrease in the MBC of bacitracin for USA300. Furthermore, bacitracin/OG combinations demonstrated similar levels of antimicrobial activity against human clinical isolates of MRSA resistant to multiple antibiotics of clinical importance. Some alkyl gallates, particularly OG, significantly increased the antimicrobial activity of bacitracin against MDR MRSA.

An important prerequisite for efficient Förster resonance energy transfer (FRET) from human serum albumin to alkyl gallate

​The formation of a stable complex by fixing alkyl gallate to HSA at an appropriate orientation and distance was an important prerequisite for efficient FRET. The specific structure of HSA helped provide the selectivity of alkyl gallate.

Redox transformations of triphenylantimony(V) catecholate complexes based on alkyl gallates

The electrochemical transformations of triphenylantimony(V) catecholate complexes containing fragments of alkyl gallates (RO(O)C–(OH)Cat)SbPh3 (R = CH3 (1), C8H17 (2), and C12H25 (3)); (RO(O)C–(OH ∙ NEt3)Cat)SbPh3 (4); and ROC(O)GallH3 (R = CH3 (5), C8H17 (6), and C12H25 (7)) in acetonitrile were studied. The electrochemical oxidation of alkyl gallates 5–7 proceeds in two irreversible stages and leads to formation of o-quinoid products. At the first stage, the oxidation of antimony(V) compounds is electrochemically quasi-reversible and leads to the formation of unstable cationic complexes. The second irreversible redox transfer results in ligand decoordination and destruction of the compounds. Three redox stages were observed for complex 4. The triethylamine-deprotonated hydroxy group is oxidized at the first electrochemical step that leads to a further intramolecular transfer, forming a stable intermediate, whose oxidation occures in quasireversible manner.

Anti- and prooxidant activity of triphenylantimony(V) catecholates derived from alkyl gallates

Antiradical and antiand prooxidant activities of the newly obtained triphenylantimony(V) catecholate complexes derived from gallic acid esters of the general formulas (RO(O)C–Cat)SbPh3 (R = Me (1), C8H17 (2), C12H25 (3)) and (MeO(O)C–(OH•NEt3)Cat)SbPh3 (4) were studied. The comparative study involving gallic acid esters of the general formula RO(O)C–GallH3 (R = Me (5), C8H17 (6), C12H25 (7)) was performed in order to evaluate the effect of organic ligands on the properties of the antimony(V) compounds. The values of EC50, the number of converted molecules of stable radical (nDPPH), as well as the relative content of oleic acid hydroperoxides confirm the antiradical and antioxidant activity of triphenylantimony(V) complexes in reactions with diphenylpicrylhydrazyl radicals and in the antioxidation of oleic acid. The influence of more active compounds 1 and 4 and ester 5 on lipid peroxidation of the rat liver homogenate of male Wistar line was determined. The membraneprotective properties were evaluated for induced hemolysis of erred blood cells as an example, and catalase activity of erythrocyte hemolysate was studied.

Antibacterial activity of alkyl gallates is a combination of direct targeting of FtsZ and permeabilization of bacterial membranes.

Alkyl gallates are compounds with reported antibacterial activity. One of the modes of action is binding of the alkyl gallates to the bacterial membrane and interference with membrane integrity. However, alkyl gallates also cause cell elongation and disruption of cell division in the important plant pathogen Xanthomonas citri subsp. citri, suggesting that cell division proteins may be targeted by alkyl gallates. Here, we use Bacillus subtilis and purified B. subtilis FtsZ to demonstrate that FtsZ is a direct target of alkyl gallates. Alkyl gallates disrupt the FtsZ-ring in vivo, and cause cell elongation. In vitro, alkyl gallates bind with high affinity to FtsZ, causing it to cluster and lose its capacity to polymerize. The activities of a homologous series of alkyl gallates with alkyl side chain lengths ranging from five to eight carbons (C5–C8) were compared and heptyl gallate was found to be the most potent FtsZ inhibitor. Next to the direct effect on FtsZ, alkyl gallates also target B. subtilis membrane integrity—however the observed anti-FtsZ activity is not a secondary effect of the disruption of membrane integrity. We propose that both modes of action, membrane disruption and anti-FtsZ activity, contribute to the antibacterial activity of the alkyl gallates. We propose that heptyl gallate is a promising hit for the further development of antibacterials that specifically target FtsZ.

Antioxidant activity of alkyl gallates and glycosyl alkyl gallates in fish oil in water emulsions: Relevance of their surface active properties and of the type of emulsifier

The antioxidant activity of gallic acid and a series of alkyl gallates (C4–C18) and glycosylated alkyl gallates (C4–C18) on fish oil-in-water emulsions was studied. Three types of emulsifiers, lecithin, Tween-20 and sodium dodecyl sulphate (SDS) were tested. A nonlinear behavior of the antioxidant activity of alkyl gallates when increasing alkyl chain length was observed for emulsions prepared with lecithin. Medium-size alkyl gallates (C6–C12) were the best antioxidants. In contrast, for emulsions prepared with Tween-20, the antioxidants seem to follow the polar paradox. Glucosyl alkyl gallates were shown previously to be better surfactants than alkyl gallates. Nevertheless, they exhibited a worse antioxidant capacity than their corresponding alkyl gallates, in emulsions prepared with lecithin or Tween-20, indicating the greater relevance of having three OH groups at the polar head in comparison with having improved surfactant properties but just a di-ortho phenolic structure in the antioxidant.

Synthesis and antiradical activity of new triphenylantimony(V) catechlolates derived from alkyl gallates

Synthesis and antiradical activity of new triphenylantimony(V) catechlolates derived from alkyl gallates