Stable isotope dilution analysis of N-acetylaspartic acid in urine by liquid chromatography electrospray ionization tandem mass spectrometry

N-acetylaspartic acid (NAA) is a specific urinary marker for Canavan disease, an autosomal recessive leukodystrophy. We developed a 'dilute and shoot' stable isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) method for determination of NAA in urine. Deuterated internal standard d(3)-NAA was added to untreated urine and the mixture was injected into the LC-MS/MS system operated in the negative ion mode. Chromatography was carried out on a C(8) minibore column using 50% acetonitrile solution containing 0.05% formic acid at a flow rate of 0.25 mL/min. The retention time was 1.6 min and the turnaround time was 2.2 min. NAA and d(3)-NAA were analyzed in multiple reaction monitoring mode. Calibrators and quality control samples were prepared in pooled control urine. The assay was linear up to 2000 micromol/L with limit of quantification at 1 micromol/L (S/N = 12). Interassay and intraassay coefficients of variation were less than 7% and recovery at three different concentrations was 98.9-102.5%. The LC-MS/MS method for NAA as described involves no extraction and no derivatization, showed no interference and gave excellent recovery with low variability and short analytical time. The method was successfully applied for the retrospective analysis of urine from 21 Canavan disease cases.     

Forensic Analysis of Textile Synthetic Fibers Using a FT-IR Spectroscopy Approach

Synthetic fibers are one of the most valuable trace lines of evidence that can be found in crime scenes. When textile fibers are analyzed properly, they can help in finding a linkage between suspect, victim, and the scene of the crime. Various analytical techniques are used in the examination of samples to determine relationships between different fabric fragments. In this exploratory study, multivariate statistical methods were investigated in combination with machine learning classification models as a method for classifying 138 synthetic textile fibers using Fourier transform infrared spectroscopy, FT-IR. The data were first subjected to preprocessing techniques including the Savitzky–Golay first derivative method and Standard Normal Variate (SNV) method to smooth the spectra and minimize the scattering effects. Principal Component Analysis (PCA) was built to observe unique patterns and to cluster the samples. The classification model in this study, Soft Independent Modeling by Class Analogy (SIMCA), showed correct classification and separation distances between the analyzed synthetic fiber types. At a significance level of 5%, 97.1% of test samples were correctly classified.     

Parasitological and Biochemical Efficacy of the Active Ingredients of Allium sativum and Curcuma longa in Schistosoma mansoni Infected Mice

The active ingredients allicin and curcumin have a wide range of actions against fungi, bacteria, and helminths. Therefore, the study was aimed to evaluate the efficacy of allicin (AL) and curcumin (CU) as antischistosomal drugs and their biochemical effects in normal and Schistosoma mansoni-infected mice. Praziquantel (PZQ) was administrated for two successive days while AL or CU was given for two weeks from the week 7th postinfection (PI). The possible effect of different regimens on Schistosoma worms was evaluated by measuring the percentage of the recovered worms, tissue egg load, and oogram pattern. Serum alanine transaminase activity and levels of triglycerides, cholesterol, and uric acid were measured. Liver tissue malondialdehyde and reduced glutathione levels besides, the activities of glutathione-S-transferase, superoxide dismutase and catalase were assessed for the oxidative/antioxidant condition. DNA electrophoresis of liver tissue was used to indicate the degree of fragmentation. There was a significant reduction in the recovered worms and egg load, with a marked change of oogram pattern in all treated groups with PZQ, AL, and CU in comparison with infected-untreated mice. PZQ, AL, and CU prevented most of the hematological and biochemical disorders, as well as significantly improved the antioxidant capacity and enhanced DNA fragmentation in the liver tissue of schistosomiasis mice compared to the infected-untreated group. These promising results suggest that AL and CU are efficient as antischistosomal drugs, and it would be beneficial to test their combination to understand the mechanism of action and the proper period of treatment leading to the best result.     

Phytochemical and in vitro screening of some Ficus and Morus spp. for hypolipidaemic and antioxidant activities and in vivo assessment of Ficus mysorensis (Roth)

Phytochemical screening of air-dried leaves and fruit juice of certain Ficus and Morus spp. have been studied. In an in?vitro study, the ethanol and hexane extracts of the investigated plants were evaluated against hyperlipidaemia by estimating the rate limiting enzyme of cholesterol biothenysis; β-hydroxy-β-methylglutaryl coenzyme A reductase (HMG-CoA reductase). The antioxidant activity was evaluated by reduction of DPPH(-) free radical. Extra phytochemical screening of Ficus extracts was undertaken, which recorded potent hypolipidaemic and antioxidant activities. The more pronounced extract, Ficus mysorensis (hexane extract), was evaluated in?vivo by estimation of the lipid profile and certain antioxidant parameters in hypercholesterolemic rats. The hexane fraction was chromatographed and six isolated compounds were identified. Furthermore, its saponifiable fraction was identified by a MS/MS technique. In conclusion, F. mysorensis recorded hypolipidaemic and antioxidant effects. Detailed studies of the isolated compounds must be undertaken for an evaluation against hypercholesterolemia and free radical elevation.     

Hypolipidaemic and antioxidant activities of Ficus microcarpa (L.) in hypercholesterolemic rats

Saponifiable and unsaponifiable fractions of Ficus microcarpa leaves hexane extract have been phytochemically studied and evaluated for its hypolipidaemic and antioxidant effects in hypercholesterolemic rats. The effect of the extract on the lipid profile was assessed by measuring the levels of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, phospho and total lipids. Lipid peroxides, glutathione and superoxide dismutase were measured as antioxidants. The work was extended to evaluate liver function indices as well as the histopathological picture of the liver after treatment. Treatment with leaves extract (500 mg kg?1 body weight) 5 times/week for 9 weeks at the same time of cholesterol administration (30 mg/0.3 mL 0.7% tween/animal) recorded an improvement of lipid profile, antioxidants, liver function enzymes and the liver histopathological picture. The lipoidal matters of the unsaponifiable fraction of the hexane extract by GC/MS led to the identification of 22 compounds, while saponifiable fraction by (MS/MS) technique led to identification of 13 unsaturated and saturated fatty acid methyl ester derivatives. It can be concluded that the hexane extract of F. microcarpa L has been proved to have hypolipidaemic and antioxidant effects in hypercholesterolemic rats through its role in counteracting LDL oxidation, enhancement of HDL synthesis and inhibition of lipid peroxidation.     

Synthesis and in vitro antimicrobial activity of some pyrazolyl-1-carboxamide derivatives

A series of 3,5-disubstituted pyrazole-1-carboxamides were obtained by treatment of chalcones with semicarbazide hydrochloride in dioxane containing sodium acetate/acetic acid as a buffer solution. N-acetyl derivatives of pyrazole-1-carboxamides were isolated in good yields either by treatment of the carboxamide derivatives with acetic anhydride or refluxing chalcones with semicarbazide in ethanol containing few drops of acetic acid to give the corresponding hydrazones. Subsequent treatment of hydrazones with acetic anhydride gave the desired N-acetyl pyrazole-1-carboxamides derivatives. When chalcones were refluxed with dioxane containing few drops of acetic acid, 4,5-dihydropyrazole-1-carboxamides were isolated, which were subsequently oxidized using 5% sodium hypochlorite in dioxane to afford pyrazole-1-carboxamides. The structures of isolated compounds were confirmed by elemental analyses and spectral methods. The isolated compounds were tested for their antimicrobial activities.     

Dibenzo[b,e][1,4]diazepin-1-Ones,Synthesis and Derivatization

Several linearly fused tricyclic 6,7,6-systems were prepared. Reaction of 1,2-diamino-4-nitrobenzene with 5,5-dimethylcyclohexan-1,3-dione gave 3-(2-amino-5-nitroaniIino)-5,5-dimethylcyclohex-2-en-1-one (8) . Reaction of 8 and its analogue 6 with various aldehydes gave 2,3,4₎5,10,11-hexahydro-3,3-dimethyl-11-substituted-1H-dibenzo[b,e][1,4]diazepin-1-ones 9 and 10 . Acetylation of 9 and 10 gave the corresponding N-acetyl derivatives. Spectral data of the products are discussed.     

New furochromone derivatives as promising in-vitro anti-proliferative agents toward HepG-2 and MCF-7 cell lines with molecular docking studies

Based on the considerable features of the multicomponent reactions (MCRs) in the field of organic and medicinal chemistry, the present work was designed to synthesize a new series of imidazole, pyridine, and pyrimidine derivatives using MCRs to obtain new anti-proliferative agent beside exploration of their interaction mechanism by molecular docking technique. MCRs of furochromone carbaldehyde 1 , benzoin, and ammonium acetate afforded the corresponding 2,4,5-trisubstituted imidazole 2 . However, MCRs of 1 with benzoin, amine derivatives, and ammonium acetate yielded the corresponding 1,2,4,5-tetrasubstituted imidazole 3a,b . In addition, pyridine 4a,b-5a,b and pyrimidine derivatives 6a,d were synthesized via condensation of 1 with different carbonyl compounds and ammonium acetate or benzyl urea, respectively. The in-vitro anti-Proliferative activities of the new furochromone derivatives were screened toward MCF-7 and HepG-2 cancer cell lines as well as the normal cell line (human normal melanocyte, HFB4) in comparison to the known anticancer drugs: 5-fluorouracil and doxorubicin using MTT assay. Compounds 5a and 5b revealed effective anti-proliferative activity against MCF-7 cell lines with IC ₅₀ 18 and 22 μg/mL, respectively, compared to 5-fluorouracil (IC ₅₀ of 13 μg/mL). However, compounds 6a-d exhibited potent activity against HepG-2 cancer cell lines of IC ₅₀ ranging from 18 to 20 μg/mL compared to doxorubicin (IC ₅₀ of 14 μg/mL). Moreover, the binding mode of the most active furochromones 5a,b and 6a-d inside the active site of the epidermal growth factor receptor (EGFR) kinase enzyme (PDB ID: 5CAV) were studied using molecular docking technique. Compounds 6b,c showed excellent docking results compared to the known EGFR inhibitors ( 4ZQ ).     

Analytical Study of Filters Dimensions and Spectral Thermal Effects on Optical Filters Operation Performance Characteristics

We study the different optical filters design considerations over wide range of the operation conditions in near infrared optical spectrum transmission region. There are many operating conditions parameters describing optical filter properties such as the amount absorbed electromagnetic radiation which depends on the operating signal wavelength; the amount of the absorbing material in the filter thickness; and the absorption coefficient of the material at that wavelength. Filter modulation depth, filtration signal quality, filter delay time, filter bit error rate, and filter correction are the major interesting performance parameters in the current study. Best candidate materials based optical filters are used which namely barium fluoride (BaF₂), and zinc selenide (ZnSe) and compared with published measured works. Our results are validated against published experimental studies and show a good agreement and matching.     

Synthesis,Photoisomerization, Antioxidant Activity,and Lipid-Lowering Effect of Ferulic Acid and Feruloyl Amides

The Ugi four-component reaction employing naturally occurred ferulic acid (FA) is proposed as a convenient method to synthesize feruloyl tertiary amides. Applying this strategy, a peptoid-like derivative of ferulic acid (FEF77) containing 2 additional hydroxy-substituted aryl groups, has been synthesized. The influence of the configuration of the double bond of ferulic acid and feruloyl amide on the antioxidant activity has been investigated thanks to light-mediated isomerization studies. At the cellular level, both FA, trans and cis isomers of FEF77 were able to protect human endothelial cord vein (HECV) cells from the oxidative damage induced by exposure to hydrogen peroxide, as measured by cell viability and ROS production assays. Moreover, in steatotic FaO rat hepatoma cells, an in vitro model resembling non-alcoholic fatty liver disease (NAFLD), the molecules exhibited a lipid-lowering effect, which, along with the antioxidant properties, points to consider feruloyl amides for further investigations in a therapeutic perspective.