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1.
J Chromatogr A ; 1725: 464949, 2024 Jun 21.
Article En | MEDLINE | ID: mdl-38688054

This study introduces an innovative needle trap device (NTD) featuring a molecularly imprinted polymer (MIP) surface-modified Zeolite Y. The developed NTD was integrated with gas chromatography-flame ionization detector (GC-FID) and employed for analysis of fuel ether oxygenates (methyl tert­butyl ether, MTBE, ethyl tert­butyl ether, ETBE, and tert­butyl formate, TBF) in urine samples. To optimize the key experimental variables including extraction temperature, extraction time, salt concentration, and stirring speed, a central composite design-response surface methodology (CCD-RSM) was employed. The optimal values for extraction in the study were found to be 51.2 °C extraction temperature, 46.2 min extraction time, 27 % salt concentration, and 620 rpm stirring speed. Under the optimized conditions, the calibration curves demonstrated excellent linearity within the range of 0.1-100 µg L-1, with correlation coefficients (R2) exceeding 0.99. The limits of detection (LODs) for MTBE, ETBE, and TBF were obtained 0.06, 0.08, and 0.09 µg L-1, respectively. Moreover, the limits of quantification (LOQs) for MTBE, ETBE, and TBF were obtained 0.18, 0.24, and 0.27 µg L-1, respectively. The enrichment factor was also found to be in the range of 98-129.The NTD-GC-FID procedure demonstrated a high extraction efficiency, making it a promising tool for urinary biomonitoring of fuel ether oxygenates with improved sensitivity and selectivity compared to current methods.


Limit of Detection , Methyl Ethers , Zeolites , Zeolites/chemistry , Humans , Methyl Ethers/urine , Methyl Ethers/chemistry , Molecularly Imprinted Polymers/chemistry , Biological Monitoring/methods , Chromatography, Gas/methods , Ethyl Ethers/urine , Ethyl Ethers/chemistry
2.
Article En | MEDLINE | ID: mdl-38640792

The aim of this study was to improve analysis of nonpolar lipidomics sample extracts using reversed phase (RP) chromatography. A 4/3/3 (v/v/v) mixture of methanol/methyl tert-butyl ether/chloroform (MeOH/MTBE/CHCl3, MMC) was chosen for sample extraction solvent based on its proven extraction capability for several lipid classes. To avoid carry over, loss of analytes and peak distortion the loops and all capillaries of the presented LC system were flushed and filled up with methanol until the analytical column. The choice of methanol was due to its weak elution strength and being infinitely miscible with MMC and several other nonpolar solvents. This allowed injection of a 100 µl sample that was 20 µl nonpolar extraction solvent diluted fivefold with methanol. All lipids of 25 lipid classes were transferred quantitatively to the column head where the online dilution of methanol was carried out with aqueous eluent for focusing the lipid analytes. The weak elution strength of methanol prevented peak distortions. The consecutive reversed phase elution resulted in remarkably narrow peaks (full width at half maximum was 0.07-0.08 min typically) and enhanced sensitivity (limit of detection usually in sub nM region) because of increased sample injection volume and narrow peaks. Calibration and quality control samples made by diluting commercial lipid standards 200-50000 times confirmed the applicability of this approach both for targeted lipid quantification and for untargeted quantitative comparison of lipids from different sources.


Lipids , Lipids/chemistry , Limit of Detection , Animals , Methanol/chemistry , Mass Spectrometry/methods , Lipidomics/methods , Reproducibility of Results , Chromatography, Reverse-Phase/methods , Chloroform/chemistry , Methyl Ethers/chemistry , Methyl Ethers/analysis , Chromatography, Liquid/methods , Linear Models , Liquid Chromatography-Mass Spectrometry
3.
Protein J ; 42(2): 112-124, 2023 04.
Article En | MEDLINE | ID: mdl-36905495

BACKGROUND: The health benefits of natural products have a long history. Chaga (Inonotus obliques) is used in traditional medicine and is an essential antioxidant for protecting the body from oxidants. Reactive oxygen species (ROS) are produced routinely due to metabolic processes. However, environmental pollution factors such as methyl tert-butyl ether (MTBE) can increase oxidative stress in the human body. MTBE is widely used as a fuel oxygenator that can harm health. The widespread use of MTBE has posed significant threats to the environment by polluting environmental resources, including groundwater. This compound can accumulate in the bloodstream by inhaling polluted air, with a strong affinity for blood proteins. The primary mechanism of MTBE's harmful effects is ROS production. The use of antioxidants may help reduce MTBE oxidation conditions. The present study proposes that biochaga, as an antioxidant, can reduce MTBE damage in the bovine serum albumin (BSA) structure. METHODS AND RESULTS: This study investigated the role of different concentrations of biochaga in the structural change of BSA in the presence of MTBE by biophysical methods such as UV-Vis, fluorescence, FTIR spectroscopy, DPPH radical inhibition method, aggregation test, and molecular docking. Research at the molecular level is critical to investigate the structural change of proteins by MTBE and the protective effect of the ideal dose (2.5 µg/ml) of biochaga. CONCLUSION: the results of spectroscopic examinations showed that the concentration of 2.5 µg/ml of biochaga has the least destructive effect on the structure of BSA in the presence and absence of MTBE, and it can play as an antioxidant.


Methyl Ethers , Serum Albumin, Bovine , Humans , Reactive Oxygen Species/metabolism , Molecular Docking Simulation , Antioxidants/pharmacology , Methyl Ethers/pharmacology , Methyl Ethers/chemistry , Methyl Ethers/metabolism
4.
Food Chem ; 400: 133988, 2023 Jan 30.
Article En | MEDLINE | ID: mdl-36088888

The present study was designed to study the effect of green solvent processing in two folds, (i) to extract valuable protein from dairy and non-dairy expired milk products and (ii) to compare extraction efficiency and quality of extracted protein using conventional (CS) and green solvents (GS). Ethyl acetate, ethanol, isopropanol, n-heptane and cyclopentyl methyl ether (CPME) were selected as the GS for the possible substitution of hexane and ethyl ether. For each respective solvent, protein recovery, structural and functional modifications were studied. Protein yield was extracted most effectively by GS n-heptane in dairy milk (5.33 ± 0.01%) with a protein purity of 39.73 ± 0.90%. Non-dairy milk and product had similar protein yield when treated with CS and GS. Total mean of extraction efficiency, structural and functional modifications across all samples showed GS solvents were statistically more effective than CS.


Methyl Ethers , Milk , 2-Propanol , Animals , Ethanol , Ethyl Ethers , Heptanes , Hexanes/chemistry , Methyl Ethers/chemistry , Solvents/chemistry
5.
Int J Mol Sci ; 22(17)2021 Sep 04.
Article En | MEDLINE | ID: mdl-34502514

In this study, we employed the copolymer poly(methyl vinyl ether-alt-maleic monoethyl ester) (PMVEMA-Es) and three fluorene-based cationic conjugated polyelectrolytes to develop fluorescent nanoparticles with emission in the blue, green and red spectral regions. The size, Zeta Potential, polydispersity, morphology, time-stability and fluorescent properties of these nanoparticles were characterized, as well as the nature of the interaction between both PMVEMA-Es and fluorescent polyelectrolytes. Because PMVEMA-Es contains a carboxylic acid group in its structure, the effects of pH and ionic strength on the nanoparticles were also evaluated, finding that the size is responsive to pH and ionic strength, largely swelling at physiological pH and returning to their initial size at acidic pHs. Thus, the developed fluorescent nanoparticles can be categorized as pH-sensitive fluorescent nanogels, since they possess the properties of both pH-responsive hydrogels and nanoparticulate systems. Doxorubicin (DOX) was used as a model drug to show the capacity of the blue-emitting nanogels to hold drugs in acidic media and release them at physiological pH, from changes in the fluorescence properties of both nanoparticles and DOX. In addition, preliminary studies by super-resolution confocal microscopy were performed, regarding their potential use as image probes.


Drug Carriers/chemical synthesis , Fluorenes/chemistry , Maleic Anhydrides/chemistry , Polyvinyls/chemistry , Antibiotics, Antineoplastic/pharmacology , Color , Doxorubicin/pharmacology , Drug Carriers/chemistry , Esters/chemistry , Fluorescence Resonance Energy Transfer/methods , Humans , Hydrogen-Ion Concentration , Methyl Ethers/chemistry , Nanogels/chemistry , Nanoparticles/chemistry , Particle Size , Polymers/chemistry , Vinyl Compounds/chemistry
6.
Int J Biol Macromol ; 179: 353-365, 2021 May 15.
Article En | MEDLINE | ID: mdl-33684431

This study aimed to fabricate polyelectrolyte complexes from water-soluble poly(ethylene glycol) methyl ether-grafted chitosan (mPEG-g-CTS) and alginate (ALG) in the absence of acetic acid. The complexes formed fibrous network macrogels when mPEG-g-CTS with short mPEG chains (mPEG750-g-CTS and mPEG2000-g-CTS) and mPEG-g-CTS:ALG weight ratios in the range from 1:0.14 to 1:1 were used. The macrogels at a weight ratio of mPEG-g-CTS:ALG of 1:1 possessed the highest elasticity with electrophoretic mobility close to 0 m2·V-1·s-1. Water uptake of the sponge-like lyophilized macrogels decreased with increasing ALG content, mPEG chain length, and degree of substitution of mPEG-g-CTS. In contrast, the polyelectrolyte complexes prepared using long mPEG chains of mPEG-g-CTS (mPEG5000-g-CTS) formed spherical nanoparticles (70-90 nm) and showed highly negative electrophoretic mobility (< -3.20 × 108 m2·V-1·s-1). The obtained mPEG-g-CTS/ALG polyelectrolyte complex hydrogels and nanoparticles have the potential to be applied as carriers for functional food additives, drugs, and bioactive compounds.


Alginates/chemistry , Biocompatible Materials , Chitosan/chemistry , Hydrogels , Nanoparticles/chemistry , Biocompatible Materials/chemical synthesis , Biocompatible Materials/chemistry , Hydrogels/chemical synthesis , Hydrogels/chemistry , Methyl Ethers/chemistry , Polyethylene Glycols/chemistry , Solubility , Water/chemistry
7.
J Chem Ecol ; 47(1): 63-72, 2021 Jan.
Article En | MEDLINE | ID: mdl-33392896

Much of our knowledge regarding the role of chemicals in species recognition in arthropods is based on a few taxonomic groups, predominantly insect pest species. To investigate the chemical underpinnings of species recognition cues in other arthropods, we conducted mate choice experiments and analyzed the chemical profiles of two species in the long-jawed spider genus Tetragnatha from allopatric populations across two different continents. In two separate bioassays, in which male T. extensa spiders were presented with either web silk or extracts from the silk of conspecific and heterospecific females, males consistently chose the silk or silk extract of conspecific females over those of heterospecifics. We examined the chemistry affecting this response using gas chromatography/mass spectrometry to analyze silk and whole-body extracts of the spiders. The major compounds in the extracts were identified as long chain aliphatic methyl ethers. The chemical profiles of the two species differed: the T. extensa profile consisted of 12,20-dimethylnonacosyl methyl ether (A), 8,14,20-trimethylnonacosyl methyl ether (B), and 6,14,20-trimethylnonacosyl methyl ether (C), while the profile of T. versicolor consisted of B and 14,20-dimethylnonacosyl methyl ether (D). Within each species, chemical profiles of females and males did not differ. Our results suggest that these methyl ethers are involved in species recognition of Tetragnatha spiders. This is the first study to propose compounds involved in species recognition in spiders.


Mating Preference, Animal/physiology , Methyl Ethers/analysis , Silk/chemistry , Spiders/chemistry , Animal Communication , Animals , Female , Male , Methyl Ethers/chemistry , Species Specificity , Spiders/physiology
8.
Comb Chem High Throughput Screen ; 24(4): 581-586, 2021.
Article En | MEDLINE | ID: mdl-32691703

BACKGROUND: Ethylene, propylene, and butylene as light olefins are the most important intermediates in the petrochemical industry worldwide. Methanol to olefins (MTO) process is a new technology based on catalytic cracking to produce ethylene and propylene from methanol. AIMS AND OBJECTIVE: This study aims to simulate the process of producing ethylene from methanol by using Aspen HYSYS software from the initial design to the improved design. METHODS: Ethylene is produced in a two-step reaction. In an equilibrium reactor, the methanol is converted to dimethyl ether by an equilibrium reaction. The conversion of the produced dimethyl ether to ethylene is done in a conversion reactor. Changes have been made to improve the conditions and get closer to the actual process design carried out in the industry. The plug flow reactor has been replaced by the equilibrium reactor, and the distillation column was employed to separate the dimethyl ether produced from the reactor. RESULT: The effect of the various parameters on the ethylene production was investigated. Eventually, ethylene is produced with a purity of 95.5 % in the improved design, and thermal integration was performed to minimize energy consumption. CONCLUSION: It was finally found according to the exothermic reaction of the dimethyl ether production, thermal integration in the process reduces the energy consumption in the heater and cooler.


Alkenes/chemical synthesis , Ethylenes/chemical synthesis , Methanol/chemistry , Catalysis , Computer Simulation , Dehydration , Hot Temperature , Kinetics , Methyl Ethers/chemistry , Models, Chemical
9.
J Chromatogr A ; 1625: 461302, 2020 Aug 16.
Article En | MEDLINE | ID: mdl-32709345

Additives are added to polymers in small concentration to achieve desired application properties widely used to tailor the properties. The rapid diversification of their molecular structures, with often only minute differences, necessitates the development of adequate chromatographic techniques. While modified silica so far is the workhorse as stationary phase we have probed the potential of porous graphitic carbon (HypercarbTM) for this purpose. The results show that the multitude of physicochemical interactions between analyte molecules and the graphitic surface enables separations of polyolefin stabilizers with unprecedented selectivity. To support the chromatographic results the adsorption capability of HypercarbTM for selected antioxidants and UV absorbers has been determined by Raman spectroscopy and argon physisorption measurements. The shift of the Graphite-band in the Raman spectra of HypercarbTM upon infusion with additives correlates with the changes in the Adsorption Potential Distributions. The results of argon physisorption measurements go hand in hand with the chronology of desorption of the additives in liquid chromatography experiments. The elution sequence can be explained by van der Waals or London forces, π-π-interactions and electron lone pair donor-acceptor interactions between the graphite surface and analyte functional groups.


Graphite/chemistry , Polymers/chemistry , Spectrum Analysis, Raman , Adsorption , Antioxidants/isolation & purification , Argon/chemistry , Chloroform/chemistry , Methyl Ethers/chemistry , Polyenes/chemistry , Porosity , Time Factors
10.
Environ Sci Process Impacts ; 22(4): 1037-1044, 2020 Apr 29.
Article En | MEDLINE | ID: mdl-32119021

We have characterized the various pathways for OH radical (OH˙) induced decomposition of tert-butyl methyl ether (MTBE) and found an oxidative pathway that leads to complete degradation under the prerequisite that OH radicals are present in excess. A simple polarizable continuum model is used to predict the behavior in an aqueous medium and the behavior is unchanged compared to that in the gas phase. The computational study has also revealed some of the fundamental aspects of hydrogen transfer from asymmetric ethers; the ˙OH assisted hydrogen abstraction has a barrier when the reaction takes place at a distance from the heteroatom, that is, at the tert-butyl group, whereas hydrogen abstraction from the methyl group proceeds without a barrier. The addition of ˙OH to (CH3)3COCH2˙ also proceeds without a barrier, and so does hydrogen abstraction from the resulting adduct ((CH3)3COCH2OH) to form (CH3)3COCH(OH)˙. However, a barrier is yet again found in the hydrogen abstraction from the latter to form (CH3)3COCH[double bond, length as m-dash]O and yet again in the formation of the formyl radical (CH3)3COC[double bond, length as m-dash]O˙ by hydrogen abstraction. The latter is the last step before the final stage of complete oxidation of MTBE to form CO2.


Hydroxyl Radical , Methyl Ethers , Methyl Ethers/chemistry , Models, Theoretical , Oxidation-Reduction
11.
PLoS One ; 15(2): e0228936, 2020.
Article En | MEDLINE | ID: mdl-32084150

A total of fifteen potential methyl t-butyl ether (MtBE)-degrading bacterial strains were isolated from contaminated soil. They have been identified as belonging to the genera Bacillus, Pseudomonas, Kocuria, Janibacter, Starkeya, Bosea, Mycolicibacterium, and Rhodovarius. Bacillus aryabhattai R1B, S. novella R8b, and M. mucogenicum R8i were able to grow using MtBE as carbon source, exhibiting different growth behavior and contaminant degradation ability. Their biocontrol ability was tested against various fungal pathogens. Both S. novella R8b and B. aryabhattai were effective in reducing the development of necrotic areas on leaves within 48 hours from Botritys cinerea and Alternaria alternata inoculation. Whereas, M. mucogenicum effectively controlled B. cinerea after 72 hours. Similar results were achieved using Pythium ultimum, in which the application of isolated bacteria increased seed germination. Only M. mucogenicum elicited tomato plants resistance against B. cinerea. This is the first report describing the occurrence of bioremediation and biocontrol activities in M. mucogenicum, B. aryabhattai and S. novella species. The production of maculosin and its antibiotic activity against Rhizoctonia solani has been reported for first time from S. novella. Our results highlight the importance of multidisciplinary approaches to achieve a consistent selection of bacterial strains useful for plant protection and bioremediation purposes.


Bacteria/isolation & purification , Biodegradation, Environmental , Methyl Ethers/toxicity , Alphaproteobacteria/isolation & purification , Alphaproteobacteria/metabolism , Bacillus/isolation & purification , Bacillus/metabolism , Bacteria/metabolism , Solanum lycopersicum/microbiology , Methyl Ethers/chemistry , Mycobacteriaceae/isolation & purification , Mycobacteriaceae/metabolism , Plant Diseases/microbiology , Rhizoctonia/growth & development , Soil , Soil Microbiology
12.
Chemosphere ; 248: 125975, 2020 Jun.
Article En | MEDLINE | ID: mdl-32007772

Stable isotopes have been widely used to monitor remediation of environmental contaminants over the last decades. This approach gives a good mechanistic description of natural or assisted degradation of organic pollutants, such as methyl tert-butyl ether (MTBE). Since abiotic degradation seems to be the most promising assisted attenuation method, the isotopic fractionation associated with oxidation and hydrolysis processes need to be further investigated in order to understand better these processes and make their monitoring more efficient. In this study, position-specific isotope effects (PSIEs) associated with permanganate oxidation and acid hydrolysis of MTBE were determined using isotope ratio monitoring by 13C Nuclear Magnetic Resonance Spectrometry (irm-13C NMR) combined with isotope ratio monitoring by Mass Spectrometry (irm-MS). The use of this Position-Specific Isotopic Analysis (PSIA) method makes it possible to observe a specific normal isotope effect (IE) associated with each of these two abiotic degradation mechanisms. The present work demonstrates that the 13C isotope pattern of the main degradation product, tert-butyl alcohol (TBA), depends on the chemical reaction by which it is produced. Furthermore, this study also demonstrates that PSIA at natural abundance can give new insights into reaction mechanisms and that this methodology is very promising for the future of modeling the remediation of organic contaminants.


Manganese Compounds/chemistry , Methyl Ethers/chemistry , Models, Chemical , Oxides/chemistry , Water Pollutants, Chemical/chemistry , Carbon Isotopes/analysis , Chemical Fractionation/methods , Hydrolysis , Oxidation-Reduction , Water Pollutants, Chemical/analysis , tert-Butyl Alcohol
13.
Molecules ; 25(3)2020 Feb 03.
Article En | MEDLINE | ID: mdl-32028571

The performance of headspace solid-phase microextraction (HS-SPME) was upgraded by easy and low-cost preparation of a new nanocomposite fiber. A polypyrrole/chromium-based metal-organic framework, PPy@MIL-101(Cr), nanocomposite was electrochemically synthesized and simultaneously coated on a steel wire as a microextraction sorbent. The morphology and chemical structure of the prepared nanocomposite was characterized by Fourier-transform infrared spectrometry (FT-IR), scanning electron microscopy (SEM), and energy dispersive X-ray analysis (EDX) techniques. The microsorbent was used for sampling of methyl-tert-butyl ether (MTBE) in solid samples, through an HS-SPME sampling strategy, followed by GC-FID measurement. The optimal experimental conditions, including extraction temperature, extraction time, and GC desorption conditions, were evaluated and optimized. The proposed procedure showed good sensitivity (limit of detection was 0.01 ng·g-1) and precision (relative standard deviation was 8.4% for six replicated analyses). The calibration curve was linear over the range of 5-40,000 ng·g-1, with a correlation coefficient of 0.994. The limit of quantification was 0.4 ng·g-1. The fabricated fiber exhibited good repeatability and reproducibility for the sampling of MTBE, with average recovery values of 88-114%. The intra-fiber and inter-fiber precisions were found to be 8.4% and 19%, respectively. The results demonstrated the superiority of the PPy@MIL-101(Cr)-coated fiber in comparison with handmade (polypyrrole, PPY) and commercial fibers (polyacrylate, PA; polydimethylsiloxane, PDMS; and divinylbenzene/carboxen/polydimethylsiloxane, DVB/CAR/PDMS) for the analysis of solid samples. The developed method was successfully employed for the analysis of MTBE in different soil samples contaminated by oil products.


Chromium , Metal-Organic Frameworks , Methyl Ethers , Nanocomposites , Polymers , Pyrroles , Soil , Chromium/chemistry , Liquid Phase Microextraction , Metal-Organic Frameworks/chemistry , Methyl Ethers/chemistry , Nanocomposites/chemistry , Nanocomposites/ultrastructure , Polymers/chemistry , Pyrroles/chemistry , Soil/chemistry , Soil Pollutants , Spectroscopy, Fourier Transform Infrared
14.
Chemosphere ; 246: 125648, 2020 May.
Article En | MEDLINE | ID: mdl-31891851

Difficulties in advanced dewatering of dewatered sludge hinder sludge reduction and resource utilization. L-DME (liquified dimethyl ether) has been recently used for dewatering, but the effect of organic matter dissolution using L-DME during desorption and dehydration on water removal is not clear. In this study, dewatered sludge from urban sewage treatment plants was used to conduct experiments in sequencing dissolution-separation reactors. The changes in the dehydration rate, bound water and various organic matter levels at different times, L-DME additions, and the temperature were measured. The results show that L-DME can remove 90% of water, 100% of lipids, and 8-12% of organic matter in dewatered sludge. L-DME was mixed with the semi-like colloidal sludge, and high separation of water was achieved by mixing the L-DME with water and dissolving the hydrophilic organic matter to convert the solid-like into a two-phase (solid and liquid) substance, which can be easily separated. The dissolution of hydrophilic organic matter such as polysaccharides and proteins by L-DME promotes the conversion of bound water into free water, which is key to total water removal.


Waste Disposal, Fluid/methods , Methyl Ethers/chemistry , Sewage/chemistry , Temperature , Water/analysis
15.
Chemosphere ; 239: 124724, 2020 Jan.
Article En | MEDLINE | ID: mdl-31505447

Combination of sulfuric acid modified bagasse activated carbon-bone biochar beads and Acinetobacter indicus screened from petroleum contaminated soil was the best condition for gaseous methyl tert-butyl ether (MTBE) removal. It was found that H2SO4 modified bagasse AC in powder form had higher adsorption capacity (989.33 mg g-1) than that in bead form (1.94 mg g-1). In addition, bone biochar in powder form (3.51 mg g-1) also had higher adsorption capacity than that in bead form (1.63 mg g-1). This was the fact that material beads contained high moisture content that inhibited the penetration of gaseous MTBE into the material. And a mixed material of H2SO4 modified bagasse AC-bone biochar beads had the highest adsorption capacity (2.22 mg g-1) compared to individual H2SO4 modified bagasse AC beads (1.94 mg g-1) and bone biochar beads (1.63 mg g-1) due to a mixed material had more rough surface and high surface area on its material. So, gaseous MTBE can penetrate through this material more easily. Although the maximum adsorption capacity of H2SO4 modified bagasse AC in powder form was the highest but microorganism cannot sustain and survive in this form for a long time. Therefore, the material beads were more suitable for microorganism to grow and degrade gaseous MTBE. Microorganism can degrade MTBE and caused no secondary wastes. Moreover, A. indicus was a novel strain for MTBE removal that has not been previously reported. Therefore, a combination of A. indicus-mixed material beads was a good choice for MTBE removal in a biofilter system.


Acinetobacter/metabolism , Cellulose/chemistry , Charcoal/chemistry , Methyl Ethers/chemistry , Acinetobacter/isolation & purification , Adsorption , Biodegradation, Environmental , Cells, Immobilized , Environmental Pollution , Gases , Methyl Ethers/isolation & purification , Methyl Ethers/metabolism , Petroleum , Soil Microbiology , Sulfuric Acids/chemistry , Waste Management/methods
16.
J Nat Prod ; 82(12): 3386-3393, 2019 12 27.
Article En | MEDLINE | ID: mdl-31809044

The protein tyrosine phosphatase (PTP) family of enzymes includes many attractive therapeutic targets, such as those in the leukocyte common antigen-related (LAR) subfamily of receptor PTPs. Synthesis and PTP inhibitory activity of illudalic acid and its methyl ether are described, with a focus on selective inhibition of LAR PTP relative to a small collection of other representative PTPs. The synthesis comprises 16 steps and provides illudalic acid in up to 12% overall yield from neopentylene-fused benzoate 1 (20 steps from commercial materials). Illudalic acid dose-dependently (measured IC50 = 2.1 ± 0.2 µM) and time-dependently inhibits LAR consistent with previous reports of covalent binding. The kinetics of LAR inhibition by illudalic acid are consistent with a two-step mechanism in which the inhibitor and enzyme first interact noncovalently (KI = 130 ± 50 µM), followed by covalent ligation at a rate kinact = 1.3 ± 0.4 min-1. The kinact/KI ratio of 104 corresponds to a t∞1/2 of 0.5 min, as discussed herein. The phenol methyl ether of illudalic acid was found to be less potent in our dose-response assays (measured IC50 = 55 ± 6 µM) but more selective for LAR, with a weaker initial noncovalent interaction and faster covalent ligation of LAR as compared to illudalic acid itself. A truncated analogue of illudalic acid that lacks the neopentylene ring fusion was found to be devoid of significant activity under our assay conditions, in contrast to previous reports. These observations collectively help inform further development of illudalic acid analogues as potent and selective inhibitors of the LAR subfamily of tyrosine phosphatases.


Coumarins/pharmacology , Enzyme Inhibitors/pharmacology , Protein Tyrosine Phosphatases/antagonists & inhibitors , Coumarins/chemistry , Dose-Response Relationship, Drug , Humans , Methyl Ethers/chemistry , Protein Tyrosine Phosphatases/metabolism , Spectrum Analysis/methods
17.
J Nat Prod ; 82(9): 2659-2663, 2019 09 27.
Article En | MEDLINE | ID: mdl-31486642

The reported characterization data for the allocolchicinoid alkaloid suhailamine, isolated from Colchicum decaisnei and known to have an erroneous structure, have been reanalyzed. This analysis has led to the current proposal that suhailamine has the same structure as N-acetylcolchinol methyl ether (NCME), an assertion that is supported by comparison with previously reported data for NCME. Suhailamine is therefore a phantom natural product, while NCME represents a naturally occurring allocolchicinoid rather than a purely synthetic entity.


Biological Products/chemistry , Colchicine/analogs & derivatives , Methyl Ethers/chemistry , Colchicine/chemistry , Molecular Structure
18.
J Appl Microbiol ; 127(5): 1468-1478, 2019 Nov.
Article En | MEDLINE | ID: mdl-31403229

AIMS: Medicinal plant-associated endophytic fungi are important sources of precious bioactive compounds, contributing more than 80% of the natural drugs for various ailments. The present study was aimed at evaluating the anticancer activity of the crystallized compound alternariol methyl ether (AME) against hepatocellular carcinoma (HCC) both in vitro and in vivo from an endophytic fungus residing in the medicinal plant Vitex negundo. METHODS AND RESULTS: The secondary metabolites from the endophytic fungus Alternaria alternata MGTMMP031 were isolated. Purification and characterization of the compound was performed and the potential compound was identified as AME. The crystal structure of AME was unambiguously confirmed by X-ray analysis. AME has been checked for its antibacterial and anticancer properties which showed its effectiveness against various bacteria and demonstrated marked anti-proliferative activity against the human HCC cells (HUH-7) both in vitro and in vivo. Mode of actions included cell cycle arrest, reducing the level of markers enzymes of liver cancer and preventing tumour growth. CONCLUSIONS: Alternariol methyl ether acts as a potential therapeutic target against HCC. The compound was isolated and the crystal structure was obtained for the first time from the endophytic fungus A. alternata MGTMMP031. In the present study, the crystallized structure of AME was obtained by slow evaporation technique. It can be concluded that AME acts as a potential therapeutic target against HCC. SIGNIFICANCE AND IMPACT OF THE STUDY: Endophytic fungi residing in the medicinal plants have strong biological significance and bioactive compounds from these fungi provide better therapeutic targets against diseases.


Alternaria/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Endophytes/chemistry , Lactones/isolation & purification , Lactones/pharmacology , Methyl Ethers/chemistry , Plants, Medicinal/microbiology , Alternaria/isolation & purification , Alternaria/metabolism , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/metabolism , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/physiopathology , Cell Cycle Checkpoints/drug effects , Crystallization , Endophytes/isolation & purification , Endophytes/metabolism , Humans , Lactones/chemistry , Lactones/metabolism , Liver Neoplasms/drug therapy , Liver Neoplasms/physiopathology , Methyl Ethers/isolation & purification , Methyl Ethers/pharmacology , Secondary Metabolism
19.
J Cell Mol Med ; 23(10): 6565-6577, 2019 10.
Article En | MEDLINE | ID: mdl-31369203

Angiogenesis is involved in many pathological states such as progression of tumours, retinopathy of prematurity and diabetic retinopathy. The latter is a more complex diabetic complication in which neurodegeneration plays a significant role and a leading cause of blindness. The vascular endothelial growth factor (VEGF) is a powerful pro-angiogenic factor that acts through three tyrosine kinase receptors (VEGFR-1, VEGFR-2 and VEGFR-3). In this work we studied the anti-angiogenic effect of quercetin (Q) and some of its derivates in human microvascular endothelial cells, as a blood retinal barrier model, after stimulation with VEGF-A. We found that a permethylated form of Q, namely 8MQPM, more than the simple Q, is a potent inhibitor of angiogenesis both in vitro and ex vivo. Our results showed that these compounds inhibited cell viability and migration and disrupted the formation of microvessels in rabbit aortic ring. The addition of Q and more significantly 8MQPM caused recoveries or completely re-establish the transendothelial electrical resistance (TEER) to the control values and suppressed the activation of VEGFR2 downstream signalling molecules such as AKT, extracellular signal-regulated kinase, and c-Jun N-terminal kinase. Taken together, these data suggest that 8MQPM might have an important role in the contrast of angiogenesis-related diseases.


Angiogenesis Inhibitors/pharmacology , Blood-Retinal Barrier/drug effects , Endothelium, Vascular/metabolism , Methyl Ethers/pharmacology , Neovascularization, Pathologic/drug therapy , Quercetin/pharmacology , Vascular Endothelial Growth Factor A/pharmacology , Animals , Blood-Retinal Barrier/pathology , Cell Line , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Endothelial Cells/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Humans , Male , Methyl Ethers/chemistry , Neovascularization, Pathologic/pathology , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-jun/metabolism , Quercetin/analogs & derivatives , Quercetin/chemistry , Rabbits , Retina/cytology , Signal Transduction/drug effects , Vascular Endothelial Growth Factor Receptor-1/metabolism , Vascular Endothelial Growth Factor Receptor-2/metabolism , Vascular Endothelial Growth Factor Receptor-3/metabolism
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