ABSTRACT
Glycogen synthase kinase 3ß (GSK-3ß) is a widely investigated molecular target for numerous diseases, and inhibition of GSK-3ß activity has become an attractive approach for the treatment of diabetes. Meridianin C, an indole-based natural product isolated from marine Aplidium meridianum, has been reported as a potent GSK-3ß inhibitor. In the present study, applying the structural-based optimization strategy, the pyrimidine group of meridianin C was modified by introducing different substituents based on the 2-aminopyrimidines-substituted pyrazolo pyridazine scaffold. Among them, compounds B29 and B30 showed a much higher glucose uptake than meridianin C (<5%) and the positive compound 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8, 16%), with no significant toxicity against HepG2 cells at the same time. Furthermore, they displayed good GSK-3ß inhibitory activities (IC50 = 5.85; 24.4 µM). These results suggest that these meridianin C analogues represent novel lead compounds with therapeutic potential for diabetes.
Subject(s)
Glucose/metabolism , Glycogen Synthase Kinase 3 beta/antagonists & inhibitors , Indoles/pharmacology , Pyrimidines/pharmacology , Urochordata/chemistry , Animals , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/isolation & purification , Enzyme Inhibitors/pharmacology , Hep G2 Cells , Humans , Indoles/chemistry , Indoles/isolation & purification , Pyrimidines/chemistry , Pyrimidines/isolation & purification , Structure-Activity Relationship , Thiadiazoles/pharmacologyABSTRACT
ATP-Binding Cassette (ABC) transporters are the main class of transmembrane transporters involved in pathogenic fungal resistance against chemotherapeutic agents. Herein we report results which show that batzelladine D (1) and norbatzelladine L (2) reverse the fluconazole resistance phenotype mediated by Pdr5p transporter on Saccharomyces cerevisiae. Both alkaloids were able to chemosensitize the Pdr5p-overexpressing strain by synergistic interaction with fluconazole. Both compounds also showed an inhibitory effect on the catalytic activity and on the intracellular accumulation of rhodamine 6G, and did not show significant in vitro mammalian cells toxicity.
Subject(s)
Alkaloids/pharmacology , Fluconazole/pharmacology , Porifera/chemistry , Pyrimidines/pharmacology , Rhodamines/antagonists & inhibitors , ATP-Binding Cassette Transporters/metabolism , Alkaloids/chemistry , Alkaloids/isolation & purification , Animals , Cells, Cultured , Dose-Response Relationship, Drug , Mice , Molecular Structure , Pyrimidines/chemistry , Pyrimidines/isolation & purification , Rhodamines/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Structure-Activity RelationshipABSTRACT
Riociguat is novel antihypertensive drug for treatment of pulmonary hypertension. As such, it is still being tested in many clinical and pharmacokinetic trials. Existing methods that determine serum riociguat and desmethylriociguat (DMR) are based solely on liquid chromatography with mass spectrometry. Therefore, we present a novel capillary electrophoresis with mass spectrometry method (CE-MS) for their determination in human serum as alternative method for ongoing trials. Complete resolution of both analytes was achieved by means of pH optimization of ammonium formate background electrolytes that are fully compatible with ESI/MS detection. Simple liquid-liquid extraction was used as sample pretreatment. The calibration dependence of the method was linear (in the range of 10-1000 ng/mL), with adequate accuracy (90.1-114.9%) and precision (13.4%). LOD and LOQ were arbitrarily set at 10 ng/mL for both analytes. Clinical applicability was validated using serum samples from patients treated with riociguat in pharmacokinetic study and the results corresponded with reference HPLC-MS/MS values. Capillary electrophoresis proved to be sensitive and selective tool for the analysis of riociguat and DMR.
Subject(s)
Electrophoresis, Capillary/methods , Pyrazoles/blood , Pyrimidines/blood , Spectrometry, Mass, Electrospray Ionization/methods , Electrolytes , Humans , Limit of Detection , Linear Models , Liquid-Liquid Extraction , Pyrazoles/chemistry , Pyrazoles/isolation & purification , Pyrazoles/pharmacokinetics , Pyrimidines/chemistry , Pyrimidines/isolation & purification , Pyrimidines/pharmacokinetics , Reproducibility of ResultsABSTRACT
The structure of 2,4-(4'-aminobenzenamine)pyrimidine (1), a pyrimidine alkaloid previously isolated from the bulbs of Scilla madeirensis (Asparagaceae, synonym Autonoë madeirensis), has been revised. These conclusions were met via comparison of reported NMR and EIMS data with those obtained from synthetic standards. The corrected structure is the antibiotic sulfadiazine (2), which has likely been isolated as a contaminant from the site of collection. The reported bioactivity of 1 as an α1-adrenoceptor antagonist should instead be ascribed to sulfadiazine. Our findings appear to show another example of an anthropogenic contaminant being identified as a natural product and emphasize the importance of considering the biosynthetic origins of isolated compounds within a phylogenetic context.
Subject(s)
Biological Products/pharmacology , Pyrimidines/pharmacology , Scilla/chemistry , Sulfadiazine/chemistry , Sulfadiazine/pharmacology , Biological Products/analysis , Biological Products/chemistry , Biological Products/isolation & purification , Magnetic Resonance Spectroscopy , Molecular Structure , Phylogeny , Plant Roots/chemistry , Pyrimidines/chemistry , Pyrimidines/isolation & purification , Sulfadiazine/analysis , Sulfadiazine/isolation & purificationABSTRACT
A new magnetic molecularly imprinted nanofiber (MMIN) nanocomposite was prepared and used to the selective extraction of nilotinib. MMIN was constructed using a novel and general method including a combination of molecular imprinting and electrospinning technology. By electrospun precursor nanofibers containing polyacrylonitrile, Fe3O4 magnetic nanoparticles, and nilotinib as the template, molecularly imprinted nanofibers were produced with a mean diameter of 500 nm and lengths up to several millimeters. The microstructure and morphology of the prepared MMIN were thoroughly investigated using techniques such as X-ray diffraction (XRD) and scanning electron microscopy (SEM). The MMIN was then used to the extraction of nilotinib. The extracted nilotinib was re-extracted and determined spectrofluorimetrically at the excitation and emission wavelengths of 271 and 335 nm, respectively. The relation between fluorescence signal for the re-extracted solution and nilotinib concentration was linear in the range 0.01-10.0 mg L-1 (n = 9) and the RSD for the determination of 1.0 and 5.0 mg L-1 nilotinib 2.75% and 1.09% (n = 3), respectively. The detection limit of the method was obtained as 0.002 mg L-1 nilotinib. The results indicated that the proposed method can be successfully applied to the determination of nilotinib in human serum samples. Graphical abstract.
Subject(s)
Magnetics , Molecular Imprinting , Nanofibers , Pyrimidines/isolation & purification , Acrylic Resins/chemistry , Humans , Limit of Detection , Microscopy, Electron, Scanning , Pyrimidines/blood , Reproducibility of Results , Spectrometry, FluorescenceABSTRACT
Using LC-MS/MS, a rapid and sensitive method for the simultaneous determination of pyraclostrobin and azoxystrobin residues in banana matrices (leaf and whole banana) and soil was established. The samples were extracted using acetonitrile and purified through C18 dispersive solid-phase extraction. The average recovery of the analytes in various matrices was in the range of 77.3%-103.9% with an RSD range of 0.9%-9.5%. The initial deposition amounts of pyraclostrobin and azoxystrobin at 2 h in the banana leaves of the mineral oil group were 1.43 and 1.31 times in Guangxi, and 2.10 and 1.81 times in Hainan for the water group, whereas those in the soil of the water group were 3.45 and 3.03 times in Guangxi, and 2.14 and 3.48 times in Hainan for the mineral oil group. The half-lives in the leaves and soil of the mineral oil group were not remarkably different from those of the water group. The terminal residue of the analytes on the whole banana was <0.02 mg/kg at 14 days after application from the two sites. The results of this work may indicate and promote the safety of using pyraclostrobin and azoxystrobin in banana production, especially with mineral oil spray adjuvants.
Subject(s)
Mineral Oil/chemistry , Musa/chemistry , Pesticide Residues , Pyrimidines , Strobilurins , Chromatography, Liquid/methods , Fruit/chemistry , Fungicides, Industrial/analysis , Fungicides, Industrial/isolation & purification , Fungicides, Industrial/pharmacokinetics , Kinetics , Limit of Detection , Linear Models , Pesticide Residues/analysis , Pesticide Residues/isolation & purification , Pesticide Residues/pharmacokinetics , Plant Leaves/chemistry , Pyrimidines/analysis , Pyrimidines/isolation & purification , Pyrimidines/pharmacokinetics , Reproducibility of Results , Soil/chemistry , Solid Phase Extraction , Strobilurins/analysis , Strobilurins/isolation & purification , Strobilurins/pharmacokinetics , Tandem Mass Spectrometry/methodsABSTRACT
Fabric phase sorptive extraction (FPSE), a recently introduced sorbent-based microextraction technique, was applied for the first time in order to achieve a simple and rapid simultaneous extraction of five common antidepressant drug residues (venlafaxine, paroxetine, fluoxetine, amitriptyline and clomipramine) from human blood serum. Elimination of protein precipitation step and minimized solvent consumption led to a sample preparation workflow compliant with the principles of green analytical chemistry (GAC). FPSE utilizes permeable and flexible fabric substrate chemically coated with a sol-gel organic-inorganic hybrid sorbent as the extraction device. Among all the membrane examined, sol-gel polycaprolactone-dimethylsiloxane-polycaprolactone coated polyester substrate presented optimum extraction efficiency and was found to be reusable for at least 30 times. The selected drugs were analyzed and detected by reversed phase high performance liquid chromatography method using gradient elution and a diode array detector operated at 235â¯nm. Limit of detection was found 0.15â¯ng⯵L-1, while good absolute recoveries (9.4-88.1%) and low relative standard deviations (≤9.2% andâ¯≤â¯11.0 for within-day and between-day precision, respectively) were obtained.
Subject(s)
Antidepressive Agents/blood , Antidepressive Agents/isolation & purification , Drug Residues/analysis , Drug Residues/isolation & purification , Solid Phase Extraction/methods , Amitriptyline/blood , Amitriptyline/isolation & purification , Chromatography, High Pressure Liquid , Humans , Pyrimidines/blood , Pyrimidines/isolation & purification , Solid Phase Extraction/instrumentationABSTRACT
To enhance the structural diversity of isoflavonoids and provide more derivatives for the biological screening, a semisynthetic mixture was generated by diversification of the crude extract of Radix puerariae (Pueraria montana var. lobata) through the chemical reaction with hydrazine hydrate. Eleven 3,4-diarylpyrazoles (1-11) and two 5-phenyl-6-benzyldihydropyridazinones (12 and 13) were isolated from the semisynthetic mixture, and their structures were identified by spectroscopic methods in combination with X-ray crystallographic analysis. Among them, nine compounds (5-13) were new derivatives. All the compounds were evaluated on the inhibitory activities against the prostate cancer cell lines LNCaP and PC3. Compounds 12 and 13 were found to exhibit much more potent inhibitory activities against the androgen dependent LNCaP cells than the androgen independent PC3 cells. Rapid synthesis of new 3,4-diarylpyrazoles and two 5-phenyl-6-benzyldihydropyridazinones with significant biological activity highlights the great potential of one-pot combinatorial modification for the diversification of natural products.
Subject(s)
Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Roots/chemistry , Pueraria/chemistry , Androgens/physiology , Antineoplastic Agents, Phytogenic/isolation & purification , Biological Products/chemistry , Biological Products/isolation & purification , Biological Products/pharmacology , Carbon-13 Magnetic Resonance Spectroscopy , Cell Line, Tumor , Crystallography, X-Ray , Drug Screening Assays, Antitumor , Humans , Male , Molecular Structure , Plant Extracts/isolation & purification , Prostatic Neoplasms/pathology , Proton Magnetic Resonance Spectroscopy , Pyrazoles/chemistry , Pyrazoles/isolation & purification , Pyrazoles/pharmacology , Pyrimidines/chemistry , Pyrimidines/isolation & purification , Pyrimidines/pharmacology , Spectrometry, Mass, Electrospray IonizationABSTRACT
The paper reports the kinetics and adsorption isotherm modeling for imidacloprid (IMIDA) and azoxystrobin (AZOXY) in rice straw (RS)/corn cob (CC) and peat (P)/compost (C) based biomixtures. The pseudo-first-order (PFO), pseudo-second-order (PSO), Elovich and intraparticle diffusion models were used to describe the kinetics. The adsorption data were subjected to the Langmuir and the Freundlich isotherms. Results (r2Adj values) suggested that the modified Elovich model was the best suited to explain the kinetics of IMIDA sorption while different models explained AZOXY sorption kinetics in different biomixtures (PFO in RS + C and RS + P; PSO in CC + P and Elovich in CC + C). Biomixtures varied in their capacity to adsorb both pesticides and the adsorption coefficient (Kd) values were 116.8-369.24 (AZOXY) and 24.2-293.4 (IMIDA). The Freundlich isotherm better explained the sorption of both pesticides. Comparison analysis of linear and nonlinear method for estimating the Freundlich adsorption constants was made. In general, r2Adj values were higher for the nonlinear fit (AZOXY = 0.938-0.982; IMIDA = 0.91-0.970) than the linear fit (AZOXY = 0.886-0.993; IMIDA = 0.870-0.974) suggesting that the nonlinear Freundlich equation better explained the sorption. The rice straw-based biomixtures performed better in adsorbing both the pesticides and can be used in bio-purification systems.
Subject(s)
Models, Chemical , Neonicotinoids/chemistry , Nitro Compounds/chemistry , Pyrimidines/chemistry , Strobilurins/chemistry , Adsorption , Composting , Diffusion , Kinetics , Neonicotinoids/isolation & purification , Nitro Compounds/isolation & purification , Oryza/chemistry , Pesticides/chemistry , Pesticides/isolation & purification , Plant Stems/chemistry , Pyrimidines/isolation & purification , Soil , Strobilurins/isolation & purification , Zea mays/chemistryABSTRACT
Extensive phytochemical analysis of different root fractions of Jatropha pelargoniifolia Courb. (Euphorbiaceae) has resulted in the isolation and identification of 22 secondary metabolites. 6-hydroxy-8-methoxycoumarin-7-O-ß-d-glycopyranoside (15) and 2-hydroxymethyl N-methyltryptamine (18) were isolated and identified as new compounds along with the known diterpenoid (1, 3, 4, and 7), triterpenoid (2 and 6), flavonoid (5, 11, 13, 14, and 16), coumarinolignan (8â»10), coumarin (15), pyrimidine (12), indole (17, 18), and tyramine-derived molecules (19â»22). The anti-inflammatory, analgesic, and antipyretic activities were evaluated for fifteen of the adequately available isolated compounds (1â»6, 8â»11, 13, 14, 16, 21, and 22). Seven (4, 6, 10, 5, 13, 16, and 22) of the tested compounds showed a significant analgesic effect ranging from 40% to 80% at 10 mg/kg in two in vivo models. Compound 1 could also prove its analgesic property (67.21%) when it was evaluated on a third in vivo model at the same dose. The in vitro anti-inflammatory activity was also recorded where all compounds showed the ability to scavenge nitric oxide (NO) radical in a dose-dependent manner. However, eight compounds (1, 4, 5, 6, 10, 13, 16, and 22) out of the fifteen tested compounds exhibited considerable in vivo anti-inflammatory activity which reached 64.91% for compound 10 at a dose of 10 mg/kg. Moreover, the tested compounds exhibited an antipyretic effect in a yeast-induced hyperthermia in mice. The activity was found to be highly pronounced with compounds 1, 5, 6, 10, 13, and 16 which decreased the rectal temperature to about 37 °C after 2 h of the induced hyperthermia (~39 °C) at a dose of 10 mg/kg. This study could provide scientific evidence for the traditional use of J. pelargoniifolia as an anti-inflammatory, analgesic, and antipyretic.
Subject(s)
Analgesics/pharmacology , Anti-Inflammatory Agents/pharmacology , Antipyretics/pharmacology , Jatropha/chemistry , Phytochemicals/pharmacology , Plant Extracts/chemistry , Analgesics/chemistry , Analgesics/isolation & purification , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Antipyretics/chemistry , Antipyretics/isolation & purification , Biogenic Monoamines/chemistry , Biogenic Monoamines/isolation & purification , Biogenic Monoamines/pharmacology , Coumarins/chemistry , Coumarins/isolation & purification , Coumarins/pharmacology , Edema/drug therapy , Edema/physiopathology , Fever/drug therapy , Fever/physiopathology , Flavonoids/chemistry , Flavonoids/isolation & purification , Flavonoids/pharmacology , Glycosides/chemistry , Glycosides/isolation & purification , Glycosides/pharmacology , Hyperalgesia/drug therapy , Hyperalgesia/physiopathology , Hyperthermia, Induced/methods , Indoles/chemistry , Indoles/isolation & purification , Indoles/pharmacology , Jatropha/metabolism , Male , Mice , Nitric Oxide/antagonists & inhibitors , Pain/drug therapy , Pain/physiopathology , Phytochemicals/chemistry , Phytochemicals/isolation & purification , Plant Roots/chemistry , Plant Roots/metabolism , Pyrimidines/chemistry , Pyrimidines/isolation & purification , Pyrimidines/pharmacology , Rats , Rats, Wistar , Secondary Metabolism , Terpenes/chemistry , Terpenes/isolation & purification , Terpenes/pharmacologyABSTRACT
For the first time, capillary electrophoresis has been successfully employed for the fast and highly efficient separations of a novel type of stereoisomers - planar rotamers (planamers) of four newly synthesized 5-nitrosopyrimidine derivatives. These derivatives can form two rotamers differing in the orientation of nitroso group due to strong intramolecular hydrogen bonds. Partial separation of rotamers of two 5-nitrosopyrimidines was achieved in alkaline 50 mM sodium tetraborate, pH 9.3, and in acidic 18.5/42 mM Tris/phosphate, pH 2.3, background electrolytes (BGEs) free of stereoselectors. To improve the separation of these rotamers and to attain the baseline or better separation of rotamers of other two 5-nitrosopyrimidines, various BGEs and different cyclodextrins-based stereoselectors were tested. The most effective, i.e. the fastest and baseline or better separations of rotamers of all analyzed 5-nitrosopyrimidines were achieved within a short time, 3.7-9.3 min, in the above alkaline or acidic BGEs using ß-cyclodextrin (ß-CD) or carboxymethyl-ß-CD as stereoselectors. Moreover, since the experiments with ß-CD resulted in good separations of rotamers of all the investigated 5-nitrosopyrimidines, the apparent binding constants of their complexes with this selector were determined from the dependence of their effective mobilities on the ß-CD concentration in the BGEs. The examined complexes were found to be relatively weak, with the apparent binding constants in the range 11.3-153.0 L/mol.
Subject(s)
Electrophoresis, Capillary/methods , Nitroso Compounds/chemistry , Pyrimidines/chemistry , beta-Cyclodextrins/chemistry , Electrolytes , Hydrogen Bonding , Hydrogen-Ion Concentration , Nitroso Compounds/analysis , Nitroso Compounds/isolation & purification , Pyrimidines/analysis , Pyrimidines/isolation & purification , StereoisomerismABSTRACT
The use of treated wastewaters (TWW) in agriculture is widening in areas suffering drought, such as southern Europe, to preserve freshwater supply for human consumption. The composition of TWW, especially concerning their organic carbon (OC) content, has been demonstrated to influence the processes governing the behavior of non-ionic pesticides in soils. Three OC-poor agricultural soils (SV, RM1 and RM3) from the province of Granada (Spain) were chosen for the assessment of the adsorption and desorption of the herbicide dimethenamid (DIM) and the fungicide fenarimol (FEN). TWW and sewage sludge extracts at different dissolved OC (DOC) concentrations (30, 90 and 300â¯mgâ¯L-1) were considered to evaluate their effect on pesticide adsorption-desorption. As expected by their properties, DIM and FEN were weakly and moderately adsorbed to the soils, respectively. Soil OC seemed to be the major factor controlling FEN adsorption, whereas the mineral fraction played a key role in DIM adsorption, especially in RM1 with high clay:OC ratio. Although TWW did not significantly modify the adsorption of pesticides, it enhanced DIM desorption from the three soils. Adsorption of FEN to SV and RM3 was directly related to the concentration of DOC, possibly due to co-sorption phenomena. Hysteretic desorption was found in all cases, indicating partially reversible adsorption. While FEN desorption was not altered by the solutions, the use of sludge extracts at the highest DOC concentration (300â¯mgâ¯L-1) enhanced DIM desorption as occurred with TWW. Interactions with DOC in solution seemed to predominate for this less hydrophobic compound, thus increasing the risk of natural waters contamination if TWW will be used.
Subject(s)
Acetanilides/chemistry , Pyrimidines/chemistry , Wastewater , Acetanilides/isolation & purification , Adsorption , Carbon , Europe , Humans , Pyrimidines/isolation & purification , Sewage , Soil , Soil Pollutants , SpainABSTRACT
Rigidins (2-6) are pyrrolopyrimidine alkaloids isolated from marine tunicates. Since their isolation, refinement of their total syntheses, and biochemical evaluation, interest toward this pyrrolo[2,3-d]pyrimidine scaffold as a medicinal candidate has been triggered. The derivatization of these natural products has led to the discovery of a novel range of 7-deazahypoxanthines, which exhibit extremely potent anticancer activity in human cancer cell lines. A major breakthrough toward the synthesis of rigidin and various rigidin analogues has been the application of multicomponent reactions (MCRs). The rapid assembly of molecular diversity and flexibility displayed by MCRs makes it an attractive strategy for the preparation of rigidin-inspired small molecules. Furthermore, a number of rigidin-like 7-deazaxanthine compounds have been reported in the literature and the popularity of implementing MCRs to construct these 7-deazaxanthines is highlighted here. It is our hope that the synthetic methods described in this chapter will result in the further generation of rigidin-inspired compounds that will move on from being "hits" into "leads" in the medicinal chemistry drug discovery pipeline and potentially into anticancer therapeutics.
Subject(s)
Alkaloids/chemical synthesis , Antineoplastic Agents/chemical synthesis , Chemistry Techniques, Synthetic/methods , Drug Discovery , Pyrimidines/chemical synthesis , Pyrroles/chemical synthesis , Alkaloids/isolation & purification , Alkaloids/pharmacology , Animals , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/pharmacology , Aquatic Organisms/chemistry , Molecular Structure , Pyrimidines/isolation & purification , Pyrimidines/pharmacology , Pyrroles/isolation & purification , Pyrroles/pharmacology , Urochordata/chemistryABSTRACT
This research article presents the preparation and characterization of monolithic capillary columns with incorporated bare fumed silica nanoparticles (FSNPs) and surface coated gluconamide FSNPs and their subsequent use in hydrophilic interaction capillary electrochromatography (HI-CEC) of small relatively polar solutes. The monolithic support was based on the in situ polymerization of glyceryl monomethacrylate (GMM) and ethylene glycol dimethacrylate (EDMA) yielding the poly(GMM-co-EDMA) monolith for the incorporation of bare and gluconamide-FNSPs. The poly(GMM-co-EDMA) monolith functioned as a true "support" for both types of polar FSNPs "stationary phases". In other words, monolithic capillary columns with "FSNPs stationary phases" were obtained in the sense that the contribution of the monolith proper to solute' retention was at its minimum. The gluconamide-FSNPs were obtained by reacting the FSNPs with the polar organosilane N-(3-triethoxysilylpropyl)gluconamide either by a pre- or on-column approach yielding p-gluconamide-FSNPs or o-gluconamide-FSNPs, respectively. While the p-gluconamide-FSNPs was coated by an oligosiloxane gluconamide layer as revealed by thermogravimetric analysis, the o-gluconamide-FSNPs are thought to be covered with a monomeric layer of gluconamide ligands as was manifested by the higher plate number obtained on the latter than on the former gluconamide-FSNPs incorporated monolithic columns. In the on-column modification process of FSNPs, the reaction was performed in a closed system whereby atmospheric water vapor are not available to cause the polymerization of the trifunctional organosilane N-(3-triethoxysilylpropyl)gluconamide. Also, the fact that the o-gluconamide-FSNPs incorporated monoliths were made from bare-FSNPs incorporated monoliths may indicate that the bare FSNPs were better dispersed into the monolithic matrix than the p-gluconamide-FSNPs, a condition that might have further contributed to the lower plate count obtained on p-gluconamide- than o-gluconamide-FSNPs incorporated monolithic columns. Overall, o-gluconamide-FSNPs stationary phases and to a lesser extent bare-FSNPs stationary phases proved useful in HI-CEC of small polar solutes, including DMF, formamide, thiourea, some phenols and nucleobases.
Subject(s)
Capillary Electrochromatography/methods , Gluconates/chemistry , Glycerides/chemistry , Methacrylates/chemistry , Nanoparticles/chemistry , Silicon Dioxide/chemistry , Dimethylformamide/isolation & purification , Formamides/isolation & purification , Hydrophobic and Hydrophilic Interactions , Phenols/isolation & purification , Polymerization , Purines/isolation & purification , Pyrimidines/isolation & purification , Thiourea/isolation & purificationABSTRACT
This study aimed at quantifying the residual amount of azoxystrobin in Swiss chard samples grown under greenhouse conditions at two different locations (Gwangju and Naju, Republic of Korea). Samples were extracted with acetonitrile, separated by salting out, and subjected to purification by using solid-phase extraction. The analyte was identified using liquid chromatography-ultraviolet detection. The linearity of the calibration range was excellent with coefficient of determination 1.00. Recovery at three different spiking levels (0.1, 0.5, and 4 mg/kg) ranged between 82.89 and 109.46% with relative standard deviation <3. The limit of quantification, 0.01 mg/kg, was considerably much lower than the maximum residue limit (50 mg/kg) set by the Korean Ministry of Food and Drug Safety. The developed methodology was successfully used for field-treated leaves, which were collected randomly at 0-14 days following azoxystrobin application. The rate of disappearance in/on Swiss chard was ascribed to first-order kinetics with a half-life of 8 and 5 days, in leaves grown in Gwangju and Naju greenhouses, respectively. Risk assessments revealed that the acceptable daily intake percentage is substantially below the risk level of consumption at day 0 (in both areas), thus encouraging its safe consumption.
Subject(s)
Beta vulgaris/chemistry , Food Safety , Fungicides, Industrial/analysis , Pesticide Residues/analysis , Pyrimidines/analysis , Strobilurins/analysis , Agriculture , Chromatography, Liquid , Fungicides, Industrial/isolation & purification , Limit of Detection , Linear Models , Pesticide Residues/isolation & purification , Pyrimidines/isolation & purification , Reproducibility of Results , Republic of Korea , Risk Assessment , Solid Phase Extraction , Strobilurins/isolation & purificationABSTRACT
BACKGROUND: Binary functional monomers, allyl-ß-cyclodextrin (allyl-ß-CD) and methacrylic acid (MAA) or allyl-ß-CD and acrylonitrile (AN), were exploited in a fabrication of molecularly imprinted polymers (MIPs) for selective recognition and large enrichment of pirimicarb from aqueous media. RESULTS: Special attention was paid to the computational simulation of the imprinting molecular and functional monomers. The morphological characteristics of MIPs made of allyl-ß-CD and MAA (M-MAA) were characterised by scanning electron microscopy. The effect of binding capacity of MAA-linked allyl-ß-CD MIPs (M-MAA) demonstrated higher efficiency than that of AN-linked allyl-ß-CD MIPs (M-AN) when tested in binding specificity. Finally, M-MAA was chosen to run through molecularly imprinted solid-phase extraction (MISPE) to analyse the spiked fresh leafy vegetables of pirimicarb. CONCLUSION: The present proposed technique is a promising tool for the preparation of the receptors which could recognise pirimicarb pesticide in aqueous media. © 2017 Society of Chemical Industry.
Subject(s)
Carbamates/chemistry , Pesticides/chemistry , Pyrimidines/chemistry , Solid Phase Extraction/methods , Water Pollutants, Chemical/chemistry , beta-Cyclodextrins/chemistry , Adsorption , Carbamates/isolation & purification , Methacrylates/chemistry , Molecular Imprinting , Pesticides/isolation & purification , Polymers/chemical synthesis , Polymers/chemistry , Pyrimidines/isolation & purification , Solid Phase Extraction/instrumentation , Water Pollutants, Chemical/isolation & purification , beta-Cyclodextrins/chemical synthesisABSTRACT
The metal-organic framework [(La0.9 Sm0.1 )2 (DPA)3 (H2 O)3 ]∞ was synthetized and characterized by X-ray diffractometry, differential thermogravimetric analysis, and infrared spectroscopy. The material was tested for the development and validation of a matrix solid-phase dispersion procedure for extraction of atrazine, bifenthrin, bromuconazole, clofentezine, fenbuconazole, flumetralin, procymidone, and pirimicarb, from peppers, with analysis using gas chromatography with mass spectrometry in the selected ion monitoring mode. The method developed was linear over the range tested (50.0-1000.0 µg/kg for procymidone and 200.0-1000.0 µg/kg for all other pesticides), with correlation coefficients ranging from 0.9930 to 0.9992. Experiments were carried out at 250.0, 500.0, and 1000.0 µg/kg fortification levels, and resulted in recoveries in the range of 52.7-135.0%, with coefficient of variation values between 5.2 and 5.4%, respectively, for [(La0.9 Sm0.1 )2 (DPA)3 (H2 O)3 ]∞ sorbent. Detection and quantification limits ranged from 16.0 to 67.0 µg/kg and from 50.0 to 200.0 µg/kg, respectively, for the different pesticides studied. The results were compared with literature data. The developed and validated method was applied to real samples. The analysis detected the presence of residues of pesticides procymidone, fenbuconazole, flumetralin, clofentezine, atrazine, and bifenthrin.
Subject(s)
Capsicum/chemistry , Lanthanoid Series Elements/chemistry , Metal-Organic Frameworks/chemistry , Pesticides/isolation & purification , Solid Phase Extraction , Aniline Compounds/chemistry , Aniline Compounds/isolation & purification , Atrazine/chemistry , Atrazine/isolation & purification , Bridged Bicyclo Compounds/chemistry , Bridged Bicyclo Compounds/isolation & purification , Carbamates/chemistry , Carbamates/isolation & purification , Chlorobenzenes/chemistry , Chlorobenzenes/isolation & purification , Furans/chemistry , Furans/isolation & purification , Gas Chromatography-Mass Spectrometry , Metal-Organic Frameworks/chemical synthesis , Nitriles/chemistry , Nitriles/isolation & purification , Pesticides/chemistry , Pyrethrins/chemistry , Pyrethrins/isolation & purification , Pyrimidines/chemistry , Pyrimidines/isolation & purification , Triazoles/chemistry , Triazoles/isolation & purificationABSTRACT
This study was undertaken to evaluate the effectiveness of several household practices (washing with water or acidic, alkaline, and oxidizing solutions, and peeling) in minimizing pesticide residue contamination of tomatoes, as well as the impact on the quality of the treated fruit. Tests were performed using two systemic fungicides (azoxystrobin and difenoconazole) and one contact fungicide (chlorothalonil). Solid-liquid extraction with low temperature partition (SLE/LTP) and liquid-liquid extraction with low temperature partition (LLE/LTP) were used to prepare the samples for pesticides determination by gas chromatography. Washing the tomatoes with water removed approximately 44% of chlorothalonil, 26% of difenoconazole, and 17% of azoxystrobin. Sodium bicarbonate (5%) and acetic acid (5%) solutions were more efficient, removing between 32 and 83% of the residues, while peeling removed from 68 to 88% of the pesticides. The washing solutions altered some fruit quality parameters, including acidity and chroma, and also caused weight loss. Acetic acid (0.15 and 5%) and hypochlorite (1%) solutions had the greatest effect on these parameters.
Subject(s)
Food Contamination/prevention & control , Food Handling/methods , Pesticide Residues/analysis , Pesticide Residues/isolation & purification , Solanum lycopersicum/chemistry , Chromatography, Gas , Dioxolanes/isolation & purification , Fungicides, Industrial/analysis , Fungicides, Industrial/isolation & purification , Liquid-Liquid Extraction , Nitriles/isolation & purification , Pyrimidines/isolation & purification , Strobilurins/isolation & purification , Triazoles/isolation & purificationABSTRACT
On screening of endolithic actinobacteria from a granite rock sample of Meghalaya for antibacterial compound, a novel antibacterial compound CCp1 was isolated from the fermentation broth of Actinomadura sp. AL2. On purification of the compound based on chromatographic techniques followed by characterization with FT-IR, UV-visible, 1H NMR, 13C NMR and mass spectrometry, the molecular formula of the compound was generated as C20H17N3O2, a furopyrimidine derivative. In vitro antibacterial activity of the compound was evaluated against both Gram positive and negative bacteria by agar well diffusion assay. The compound had lowest MIC (2.00 µg/ml) for Bacillus subtilis and highest MIC (> 64 µg/ml) for Staphylococcus epidermidis and Pseudomonas aeruginosa. The study revealed that the compound has potential antibacterial activity. The mode of action of the antibacterial compound was evaluated through in silico studies for its ability to bind DNA gyrase, 30S RNA molecules, OmpF porins and N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU). The antibacterial compound demonstrated more favorable docking with DNA gyrase, 30S RNA molecules and OmpF porins than GlmU which support the antibacterial compound CCp1 can be as a promising broad spectrum antibiotic agent with "multitarget" characteristics.
Subject(s)
Actinobacteria/growth & development , Anti-Bacterial Agents/chemistry , Furans/chemistry , Pyrimidines/chemistry , Actinobacteria/metabolism , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Bacillus subtilis/drug effects , Computer Simulation , Fermentation , Furans/isolation & purification , Furans/pharmacology , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Models, Molecular , Molecular Docking Simulation , Pseudomonas aeruginosa/drug effects , Pyrimidines/isolation & purification , Pyrimidines/pharmacology , Spectroscopy, Fourier Transform Infrared , Staphylococcus epidermidis/drug effectsABSTRACT
Radiosynthesis and evaluation of [11C]GSK1838705A in mice using microPET and determination of specificity in human GBM UG87MR cells are described herein. The radioligand was synthesized by reacting desmethyl-GSK1838705A with [11C]CH3I using GE FX2MeI module in â¼5% yield (EOS), >95% radiochemical purity and a specific activity of 2.5±0.5Ci/µmol. MicroPET imaging in mice indicated that [11C]GSK1838705A penetrated blood brain barrier (BBB) and showed retention of radiotracer in brain. The radioligand exhibited high uptake in U87MG cells with >70% specific binding to IGF1R. Our experiments suggest that [11C]GSK-1838705A can be a potential PET radiotracer for the in vivo quantification of IGF1R expression in GBM and other brain tumors.