Synthesis,SAR and in vitro therapeutic potentials of thiazolidine-2,4-diones

Background

Thiazolidinedione is a pentacyclic moiety having five membered unsaturated ring system composed with carbon, oxygen, nitrogen and sulfur molecules at 1 and 3 position of the thiazole ring and widely found throughout nature in various form. They favourably alter concentration of the hormones secreted by adipocytes, particularly adiponectin. They also increase total body fat and have mixed effects on circulating lipids. Thiazolidinedione nucleus is present in numerous biological moieties and has different pharmacological activities likes, e.g. antimalarial, antimicrobial, antimycobacterial, anticonvulsant, antiviral, anticancer, anti-inflammatory, antioxidant, anti-HIV (human immunodeficiency virus) and antituberculosis.

Results and discussion

The synthesized compounds were screened for their in vitro antimicrobial potential against Gram (positive and negative) bacterial and fungal strains by tube dilution technique. In this series, compound 10 exhibited significant antimicrobial activity against B. subtilis and S. aureus with MIC?=?4.2?×?10^?2 µM/ml, compound 15 showed significant activity against K. pneumonia with MIC?=?2.60?×?10^?2 µM/ml and compound 4 displayed potent antibacterial activity against E. coli with MIC?=?4.5?×?10^?2 µM/ml. Compound 10 had most potent antifungal activity against C. albicans and A. niger with MIC?=?4.2?×?10^?2 µM/ml. Compounds 12 and 15 were found as most active antidiabetic agents having IC₅₀?=?27.63 μg/ml and 22.35 μg/ml, respectively, using DPPH assay. Antioxidant activity results indicated that compounds 3 and 9 displayed good antioxidant agent with IC₅₀?=?29.04 μg/ml and 27.66 μg/ml respectively, using α amylase assay.

Conclusion

All the synthesized derivatives exhibited good antimicrobial, antidiabetic and antioxidant activities using specific methods then compared with mentioned standard drugs. Especially, compounds 3, 4, 9, 10, 12 and 15 displayed highest activity. Structure activity relationship demonstrated that presence of electron withdrawing group (o-NO₂, p-Cl, p-Br) enhanced the antibacterial activity against E. coli as well as increased the antioxidant activity while the presence of electron releasing group (o/p-OCH₃, 3,4,5-trimethoxy) enhanced the antibacterial activity against S. aureus, B. subtilis, S. typhi, K. pneumonia, C. albicans and A. niger as well as the antidiabetic activity.

     

Bacterio- and lymphocytotoxicity of silver nanocomposite with sulfated arabinogalactan

The antibacterial activity and cytotoxicity of the silver-containing drug, which is zerovalent metallic silver nanoparticles stabilized by sulfated arabinogalactan, towards human lymphocytes were evaluated. The bacteriostatic concentration towards E. coli ATCC 25922, E. coli ESBL1224, S. aureus MRSA34R, S. aureus ATCC 29213, and P. aeruginosa ATCC 27853 and hospital strains E. coli, P. aeruginosa, and P. mirabilis ranges from 3 to 50 μg mL^?1. Their bactericidal activity varies from 5 to 100 μg mL^?1, and the concentration of the nanocomposite toxic to isolated human peripheral blood lymphocytes is 5 μg m^L?1.     

Synthesis,antifungal and insecticidal activity of novel [1,2,4]triazolo[4,3-<Emphasis Type="Italic">a</Emphasis>]pyridine derivatives containing a sulfide substructure

A series of [1,2,4]triazolo[4,3-a]pyridine derivatives bearing a sulfide substructure was designed, synthesized and characterized via ¹H·NMR, ¹³C·NMR, IR and elemental analyses. Bioassay Results indicated some of the derivatives displayed good fungicidal activity on Rhizoctonia cerealis, moderated insecticidal activity against Plutella xylostella and good insecticidal activity on Helicoverpa armigera. The inhibitory effects of compounds 4g and 4u against Rhizotonia cerealis were 70.9% at 50 μg mL^?1; the IC₅₀ values of compounds 4d and 4s against Plutella xylostella were 43.87 and 50.75 μg mL^?1, respectively. And the IC₅₀ values of compounds 4d, 4q, and 4s on Helicoverpa armigera were 58.3, 77.14 and 65.31 μg mL^?1, respectively, which were better than that of commercial chlorpyrifos (103.77 μg mL^?1).     

Bioactive compounds from <Emphasis Type="Italic">Smilax excelsa</Emphasis> L.

Phytochemical investigation of EtOAc extract of Smilax excelsa has led to isolation and structure elucidation of five compounds. The structures of these compounds are established by different spectroscopic techniques including 1D and 2D-NMR, HRMS and ECD spectroscopy. The compounds were: solanesol (1), violasterol A (2), trans-resveratrol (3), 5-O-caffeoylshikimic acid (4) and 6-O-caffeoyl-β-d-fructofuranosyl-(2-1)-α-d-glucopyranoside (5). The configuration of compound 2 was established by electronic circular dichroism (ECD) spectroscopy. Meanwhile the cytotoxicity and antibacterial activity of the compounds were evaluated by MTT and MIC assays. Compounds 1 and 2 showed promising inhibition on MCF-7 cell line with IC₅₀ of 161.6 and 190.0 µM, respectively. Also compounds 2 and 3 illustrated activity against Staphylococcus aureus with MIC values of 142.5 and 136.9 µM, respectively.     

Synthesis and antibacterial evaluation of novel Schiff base derivatives containing 4(3<Emphasis Type="Italic">H</Emphasis>)-quinazolinone moiety

A series of novel Schiff base derivatives containing 4(3H)-quinazolinone moiety were synthesised and their antibacterial activities against tobacco and tomato bacterial wilts evaluated in vitro. Out of the synthesised compounds, 5g, 5j, 5n, 5m and 5p exhibited excellent antibacterial activities against tobacco bacterial wilt, with half maximal effective concentrations (EC50): 160.34, 158.03, 125.94, 148.09 and 133.67 (all in εg mL^?1), respectively, which were better than the EC50 of thiodiazole–copper (216.70 εg mL^?1). Compounds 5j, 5n and 5o also showed good antibacterial activities against tomato bacterial wilt, with EC50 of 95.20, 90.03 and 83.21 (all in εg mL^?1) respectively, which were better than the EC50of thiodiazole–copper (99.80 εg mL^?1). These compounds may prove to be useful as potential antibacterial agents.     

Newly synthesized indolizine derivatives — antimicrobial and antimutagenic properties

A series of indolizine derivatives have been synthesized and subjected to antibacterial screening studies. Antibacterial activity of 21 derivatives was investigated against Staphylococcus aureus, Mycobacterium smegmatis, Salmonella typhimurium and Escherichia coli; also, the sensitivity of model yeast Candida parapsilosis and some model filamentous fungi Aspergillus fumigatus, Alternaria alternata, Botrytis cinerea and Microsporum gypseum was tested. Newly synthesized indolizine derivatives have shown selective toxicity to Gram-positive bacteria S. aureus and were also considered to be able to inhibit the acidoresistant rod M. smegmatis. Derivative XXI has shown the highest inhibition effect with the bacteriostatic effect on the cells at the concentration of 25 µg mL^?1. The best antifungal activity has been detected in the presence of derivative XIII. Derivative XIII did also affect the morphology of hyphal tips of B. cinerea, which led to enhanced ramification of hyphae. Finally, the antimutagenic activity of derivatives was investigated. Significant antimutagenic activity was registered in case of derivative VIII. The number of induced revertants by mutagen [2-(5-nitrofuryl)acrylic acid] was decreased almost to the level of spontaneous revertants in the lowest applied concentration (50 µg per plate).     

Synthesis and biological activities of novel quinazolinone derivatives containing a 1,2,4-triazolylthioether moiety

A series of novel quinazolinone derivatives containing a 1,2,4-triazolylthioether moiety were synthesised and their antimicrobial activities were evaluated. All the target compounds were characterised by ¹H NMR, ¹³C NMR, ESI-MS, IR and elemental analyses. The single crystal structure of 3-((5-((2-fluorobenzyl)thio)-4-phenyl-4H-1,2,4-triazol-3-yl)methyl)quinazolin-4(3H)-one (VIIi) was also determined. The preliminary bioassays indicated that some of the target compounds possessed good antimicrobial activities. For example, 3-((4-phenyl-5-((4-(trifluoromethyl)benzyl)thio)-4H-1,2,4-triazol-3-yl)methyl)quinazolin-4(3H)-one (VIIs) exhibited the best inhibitory effect against Xanthomonas oryzae pv. oryzae and Xanthomonas axonopodis pv. citri with the half-effective concentration (EC₅₀) values of 47.6 μg mL^?1 and 22.1 μg mL^?1, respectively, which were superior to the commercial bactericide, bismerthiazol. Meanwhile, 3-((5-((4-chlorobenzyl)thio)-4-phenyl-4H-1,2,4-triazol-3-yl)methyl)quinazolin-4(3H)-one (VIIh) exhibited better fungicidal activities against Pellicularia sasakii and Colletotrichum capsici at the concentration of 50 μg mL^?1, in comparison with the commercial fungicide, hymexazol.     

Synthesis,Crystal Structure,and Antibacterial Activity of a Dinuclear Oxidovanadium(V) Complexes Derived from 2-[(2-Methylaminoethylimini)methyl]- 4-Trifluoromethoxyphenol

A new dinuclear oxidovanadium(V) complex, [V₂O₂(μ-O)₂L₂], where L is the monoanionic form of 2-[(2-methylaminoethylimini)methyl]-4-trifluoromethoxyphenol (HL), was prepared and characterized by IR, UV-Vis and ¹H NMR spectra, as well as single crystal X-ray diffraction (CIF file CCDC no. 1567062). The complex crystallizes as the monoclinic space group P2₁/c with unit cell dimensions a = 12.974(3), b = 6.572(2), c = 17.205(3) Å, β = 107.300(3)°, V = 1400.7(5) ų, Z = 2, R₁ = 0.0879, wR₂ = 0.1208, GOOf = 1.068. X-ray analysis indicates that the complex is a centrosymmetric dinuclear oxidovanadium(V) species with the V atoms in octahedral coordination. The Schiff base and the complex were evaluated for their antibacterial (Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas fluorescence) activities. The complex has the most activity against B. subtilis with the MIC value of 1.2 μg mL^–1.     

Synthesis and in vitro antibacterial evaluation of 6-substituted 4-amino-pyrazolo[3,4-<Emphasis Type="Italic">d</Emphasis>]pyrimidines

Pyrazolo[3,4-d]pyrimidines are one of the most important classes of fused heterocyclic compounds which exhibit a broad range of biological and medicinal properties. They are known as anticancer, antifungal, antibacterial, antiviral and anti-inflammatory agents. In this study, some new 6-substituted 4-amino-pyrazolo[3,4-d]pyrimidine derivatives were prepared via reaction of 5-amino-3-methyl-1-phenyl-1H-pyrazole-4-carbonitrile with various nitriles in the presence of sodium ethoxide as catalyst. The inhibitory properties of synthesized compounds were studied according to CLSI guidelines against some pathogenic bacteria including four gram-positive strains (Streptococcus pyogenes, Staphylococcus aureus, Bacillus cereus and Bacillus subtilis subsp. spizizenii) and three gram-negative strains (Pseudomonas aeruginosa, Shigella flexneri and Salmonella enterica subsp. enterica). The antibacterial effects of all derivatives were compared with those of antibiotics belonging to different classes. The values were reported as inhibition zone diameter (IZD), minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The effect of substituents on the biological activity of derivatives was discussed as well. The inhibitory effect of compound 6a, was shown to be the most, with MIC values in the range of 32–4096 μg/mL. Since most of the synthesized compounds were effective against Streptococcus pyogenes and Pseudomonas aeruginosa, they can be considered as inhibitors of these two bacteria.     

Teicoplanin-functionalized magnetic beads for detection of <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> via inhibition of the luminol chemiluminescence by intracellular catalase

An affinity-based protocol is described for the detection of Staphylococcus aureus (S. aureus). It is utilizing teicoplanin-functionalized magnetic beads as carriers. Teicoplanin, which binds to the walls of cells of S. aureus via five hydrogen bonds, acts as the recognition agent. Captured S. aureus is magnetically separated from the sample matrix and then specifically lysed by lysostaphin which cleaves the cross-linking pentaglycine bridges of peptidoglycan in the cell wall. Lastly, S. aureus is quantified via the inhibitory effect of released intracellular catalase on a chemiluminescent (CL) system composed of peroxidase, luminol, H₂O₂ and p-iodophenol because catalase decomposes H₂O₂. S. aureus can be detected with CL response in the 140 to 1.4?×?10⁷ CFU·mL^?1 concentration range and a detection limit as low as 47 CFU·mL^?1 at a signal-to-noise ratio of 3. The method was evaluated by analyzing spiked samples including milk, human urine and saline injection solutions. The reliability was demonstrated by a recovery test and by comparison with a conventional plate counting method.

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Graphical abstract An antibiotic-affinity protocol is developed to detect Staphylococcus aureus (S. aureus) by utilizing teicoplanin-functionalized magnetic beads (Teic-MBs) as carriers. S. aureus can be quantified by measuring the inhibition of luminol chemiluminescence (CL) signal by intracellular catalase.

     

Synthesis,crystal structures,and antibacterial activities of Schiff base nickel(II) and cadmium(II) complexes with tridentate Schiff bases

Reaction of tridentate Schiff bases with nickel and cadmium salts in methanol afforded two new mononuclear complexes, [Ni(L¹)₂] (I) and [Cd(L²)₂] (II), where L¹ and L² are the anions of 2-bromo-4-chloro-6-[(3-dimethylaminopropylimino)methyl]phenol (HL¹) and 2-bromo-4-chloro-6-[(3-morpholin-4-ylpropylimino)methyl]phenol (HL²), respectively. The complexes were characterized by singlecrystal X-ray diffraction (CIF files CCDC nos. 1428653 (I) and 1428654 for (II)), FT-IR, and elemental analysis. Complex I crystallizes in the monoclinic space group P2 ₁/c, with a = 8.8216(8), b = 14.0424(8), c = 11.8687(12) Å, β = 111.238(2)°, V = 1370.4(2) ų, Z = 2. Complex II crystallizes in the monoclinic space group P2 ₁/n, with a = 9.6774(4), b = 15.8970(6), c = 20.3144(7) Å, β = 90.408(2)°, V = 3125.1(2) ų, Z = 4. The metal atoms in the complexes are coordinated by two tridentate Schiff base ligands, forming octahedral coordination. The free Schiff bases and the complexes were assayed for antibacterial activities. Both complexes are more active against the bacteria than the free Schiff bases. Complex II has the MIC value of 0.39 μg mL^–1 against Bacillus subtilis.     

Synthesis,characterization, antimicrobial activity and ultrastructure of the affected bacteria of new quinoline compounds

The reaction on 8-hydroxy quinoline-7-aldehyde azo compounds (HL _n ) (where n = 1–5) with 4-amino-1,2-dihydro-2,3-dimethyl-1-phenylpyrazol-5-one to obtain HL _n (where n = 6–10) have been characterized by means of TLC, melting point and spectral data, such as IR, ¹H NMR, mass spectra and thermal studies. The X-ray diffraction patterns of two starting materials 8-hydroxy quinoline-7-aldehyde (start 1), 4-amino-1,2-dihydro-2,3-dimethyl-1-phenylpyrazol-5-one (start 2) and the ligands (HL_5,10) are investigated in powder form. All the ligands have been screened for their antimicrobial activity against four local bacterial species, two Gram-positive bacteria (Bacillus cereus and Staphylococcus aureus) and two Gram-negative bacteria (Escherichia coli and Klebsiella pneumoniae) as well as against four local fungi; Aspergillus niger, Alternaria alternata, Penicillium italicum and Fusarium oxysporium. The results show that the azo ligands (HL _n ) (where n = 1–5) have no antimicrobial activity against bacteria and fungi while most azomethine ligands (HL _n ) (where n = 6–10) are good antibacterial agents against E. coli and K. pneumoniae as well as antifungal agents against P. italicum and A. alternata. The results were compared to standard substances (start 1) and (start 2). Among the azomethine ligands, HL₁₀ was the most effective against the most microorganisms tested. The size of clear zone was ordered as p-(OCH₃ < CH₃ < H < Cl < NO₂) as expected from Hammett’s constant (σ ^R ). Also, the ultrastructure study of the affected bacteria confirmed that HL₈ is good antibacterial agent against E. coli and S. aureus.     

Synthesis and in vitro anticancer,antibacterial, and antioxidant studies of unsymmetrical Schiff base derivatives of 4-[(1<Emphasis Type="Italic">E</Emphasis>)-<Emphasis Type="Italic">N</Emphasis>-(2-aminoethyl)ethanimidoyl]benzene-1,3-diol

Schiff bases such as 2-hydroxy-1-(4-hydroxyphenyl)ethanone (DHAP) and its derivatives have attracted attention because they are useful in design and development of novel organic compounds for potential pharmaceutical applications. In this work, a series of 4-[(1E)-N-(2-aminoethyl)ethanimidoyl]benzene-1,3-diol (4a–h) Schiff bases were synthesized by reaction of ethylenediamine, DHAP, and appropriate aldehyde moieties. The compositions of the prepared compounds were established using elemental analysis and Fourier-transform infrared (FTIR) and ultraviolet–visible (UV–Vis) spectroscopies. The compounds were screened against three Gram-positive and three Gram-negative bacteria, and the results compared with standard drugs ciprofloxacin and amoxicillin. Compounds 4g, 4h were found to have higher activity against Staphylococcus aureus with minimum inhibitory concentration (MIC) value of 2.5 mg/mL, while compounds 4f and 4h inhibited Escherichia coli with MIC values of 2.5 and 5 mg/mL, respectively. The IC₅₀ values of compounds 4a–h for scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical ranged from 2.63 ± 0.79 to 3.85 ± 0.83 µM with good correlation coefficient of R ² = 0.957–0.994. In vitro anticancer screening of the compounds showed that compounds 4f, 4h, and parthenolide efficiently affected cell viability of cancer cell line MCF-7 with IC₅₀ values of 4.10 ± 1.32, 4.01 ± 2.26, and 0.44 ± 2.02 µM, respectively.     

Polyphenols,radical scavenger activity,short-chain organic acids and heavy metals of several plants extracts from “Bucharest Delta”

Some plants collected (Mentha aquatica, Bidens tripartita and Ambrosia artemisiifolia) from an unusual habitat developed in recent years in Bucharest (the so-called “Bucharest Delta”) and the contents of polyphenolic compounds, short-chain organic acids and heavy metals, and radical scavenger activity, were determined. 12 polyphenolic compounds and 7 short-chain organic acids were quantified using high-performance liquid chromatography and capillary electrophoresis; Mentha aq. extracts presented the highest levels of rosmarinic acid (1.58 mg g^?1) and ferulic acid (2.84 mg g^?1) and Bidens extracts presented the highest concentrations of chlorogenic acid (0.44 mg g^?1); the same extracts contain the most important levels of luteolin (0.52 mg g^?1) or other flavonoids. All the heavy metals detected in the plants studied were found in very low levels (the highest was Pb(II) in Mentha aquatica, (12.84 ± 0.48) µg kg^?1). The study sought to identify the active compounds and some contaminants in plants collected from the “Bucharest Delta” with the intention of eventual exploitation of the habitat and to enhance the knowledge of such human-modified ecosystems.     

Synthesis of novel 1,3,4-oxadiazole derivatives containing diamides as promising antibacterial and antiviral agents

In this paper, a variety of novel 1,3,4-oxadiazole derivatives possessing diamides were synthesized and tested for their antibacterial and antiviral activity. Preliminary antibacterial assays indicated that some intermediates and title compounds displayed excellent inhibition effects against plant pathogens Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac). Further studies revealed that compound H15 exhibited the strongest activities against Xoo and Xac with minimal EC₅₀ values of 0.7 and 5.9 μg/mL, respectively. Antiviral bioassays suggested that some of these structures displayed appreciable curative activities and moderate protective effects against tobacco mosaic virus (TMV) in vivo. Among them, compound H8 exerted the best chemotherapeutic effect against TMV with the curative rate of 60.0% at 500 µg/mL, which was comparable with those of commercial agricultural antiviral agent ningnanmycin (54.2%). Given their significant biological activities, this kind of compound could serve as new leading compounds in the study of antibacterial and antiviral chemotherapy.     

Separation and Quantification of Enkephalin and Vasopressin Related Peptides in Reversed-Phase Capillary Liquid Chromatography

A method for determination of some biologically active penta- and nona-peptides under isocratic conditions in capillary liquid chromatography was developed. Separation system consisting of XTerra C18 stationary phase and mobile phase composed of a mixture of acetonitrile with 0.1% trifluoroacetic acid (TFA) and water with 0.1% TFA in the ratios 75/25 (v/v) and 85/15 (v/v) was suitable not only for a good resolution of enkephalin and vasopressin related peptides, respectively, but it also enabled separation of the respective biopeptides from other constituents of human urine. Calibration curves for the studied peptides were linear in the measured concentration range from 1.00 to 1.57×10^?2 mg mL^?1. The limit of detection and limit of quantification were in the range of units of μg mL^?1 and tens of μg mL^?1, respectively; slightly higher values were obtained for nonapeptides. Determination of certain biologically active peptides in urine can serve in future as a tool for diagnosis of various diseases, e.g. autism.     

Synthesis,characterization, molecular docking,analgesic, antiplatelet and anticoagulant effects of dibenzylidene ketone derivatives

In this study dibenzylidene ketone derivatives (2E,5E)-2-(4-methoxybenzylidene)-5-(4-nitrobenzylidene) cyclopentanone (AK-1a) and (1E,4E)-4-(4-nitrobenzylidene)-1-(4-nitrophenyl) oct-1-en-3-one (AK-2a) were newly synthesized, inspired from curcuminoids natural origin. Novel scheme was used for synthesis of AK-1a and AK-2a. The synthesized compounds were characterized by spectroscopic techniques. AK-1a and AK-2a showed high computational affinities (E-value >???9.0 kcal/mol) against cyclooxygenase-1, cyclooxygenase-2, proteinase-activated receptor 1 and vitamin K epoxide reductase. AK-1a and AK-2a showed moderate docking affinities (E-value >???8.0 kcal/mol) against mu receptor, kappa receptor, delta receptor, human capsaicin receptor, glycoprotein IIb/IIIa, prostacyclin receptor I₂, antithrombin-III, factor-II and factor-X. AK-1a and AK-2a showed lower affinities (E-value >???7.0 kcal/mol) against purinoceptor-3, glycoprotein-VI and purinergic receptor P₂Y₁₂. In analgesic activity, AK-1a and AK-2a decreased numbers of acetic acid-induced writhes (P?<?0.001 vs. saline group) in mice. AK-1a and AK-2a significantly prolonged the latency time of mice (P?<?0.05, P?<?0.01 and P?<?0.001 vs. saline group) in hotplate assay. AK-1a and AK-2a inhibited arachidonic acid and adenosine diphosphate induced platelet aggregation with IC₅₀ values of 65.2, 37.7, 750.4 and 422 µM respectively. At 30, 100, 300 and 1000 µM concentrations, AK-1a and AK-2a increased plasma recalcification time (P?<?0.001 and P?<?0.001 vs. saline group) respectively. At 100, 300 and 1000 µg/kg doses, AK-1a and AK-2a effectively prolonged bleeding time (P?<?0.001 and P?<?0.01 vs. saline group) respectively. Thus in-silico, in-vitro and in-vivo investigation of AK-1a and AK-2a reports their analgesic, antiplatelet and anticoagulant actions.     

Determination of mycotoxins,alkaloids, phytochemicals,antioxidants and cytotoxicity in Asiatic ginseng (Ashwagandha,Dong quai, <Emphasis Type="Italic">Panax ginseng</Emphasis>)

Mycotoxins and selected hazardous alkaloids in the medicinal plants (Panax ginseng, Angelica sinensis, and Withania somnifera) and dietary supplements were determined. Purine alkaloids were found in majority of samples; however, isoquinoline alkaloids were less abundant than indole. The predominant alkaloids appear to be caffeine (purine group), harman (indole group) and berberine (isoquinoline). Examined medicinal plants and dietary supplements were contaminated by mycotoxins (especially ochratoxin A 1.72–5.83 µg kg^?1), and many species of mold (e.g. Cladosporium, Eurotium, Aspergillus, Rhizopus, Penicillium). MTT cytotoxicity tests revealed that plant and supplements extracts exhibited medium or high cytotoxicity (only Dong quai—low). Moreover, antioxidant activity, total phenolics content and selected phytochemicals were analyzed by spectrophotometric and chromatographic methods. Quercetin and rutin were predominant flavonols (1.94-9.51 and 2.20–7.28 mg 100 g^?1, respectively). Analysis of phenolic acids revealed—gallic acid, as the most abundant, except Panax ginseng, where ferulic acid was prevailing. The results were analyzed by chemometric methods (cluster analysis, ANOVA).     

Quantitative Determination of Carisoprodol and its Metabolites in Equine Urine and Serum by Liquid Chromatography-Tandem Mass Spectrometry

Cefuroxime is a broad-spectrum second-generation bactericidal cephalosporin antibiotic active against β-lactamase-producing strains. Anti-cefuroxime, the geometric isomer of cefuroxime, might be present in cefuroxime dosage forms as a process-related impurity and possible degradation product. In the work discussed in this paper a precise and sensitive micellar liquid chromatographic (MLC) method for stability testing of cefuroxime axetil and anti-cefuroxime axetil in tablets, using benzoic acid as internal standard, was developed and validated. MLC was performed on an XTerra C₁₈ reversed-phase column at 50 °C with 8:92 (v/v) acetonitrile–20 mM sodium dodecyl sulphate, pH 2.5, as mobile phase at a flow rate of 1.5 mL min^?1. Detection was at 280 nm. Under these conditions the retention time and retention factor were of 6.65 min and 4.57, respectively, for cefuroxime axetil and 11.45 min and 8.59, respectively, for anti-cefuroxime axetil, indicating that the compounds were well separated. RSD values for quantification of cefuroxime axetil and anti-cefuroxime axetil were 0.39 and 1.7%, respectively, indicating the precision of the MLC method was good. The method is sensitive—LOD=0.5 μg mL^?1 and LOQ=1.5 μg mL^?1 for anti-cefuroxime axetil—and reproducible, with good recovery values.     

Determination of migrated phthalic acid residues into edible oils using a green mode of air-assisted liquid–liquid microextraction followed by high-performance liquid chromatography–diode array detector

In this study, for the first time, an organic solvent-free air-assisted liquid–liquid microextraction method has been reported for the extraction and preconcentration of phthalic acids (o-phthalic acid, m-phthalic acid, and p-phthalic acid) from edible oil samples. The method is based on the repeated aspirating/injection of an alkaline aqueous solution and the oil sample mixture in a conical bottom centrifuge tube to form a cloudy solution. After phase separation by centrifuging, the sedimented phase is directly analyzed by high-performance liquid chromatography–diode array detection. Under the optimum extraction conditions, the method showed low limits of detection and quantification between 0.11–0.29 and 0.28–0.91 ng mL^?1, respectively. Extraction recoveries and enrichment factors were from 81 to 97% and 406 to 489, respectively. The relative standard deviations for the analysis of 5 ng mL^?1 of each analyte were less than 5.9% for intraday (n = 6) and interday (n = 5) precisions. Finally, different oil samples were successfully analyzed using the proposed method and m-phthalic acid, and p-phthalic acid were determined in some of them at ng mL^?1 level.