BackgroundThe dry root of Salvia miltiorrhiza Bunge (Danshen in Chinese) is an used-widely traditional Chinese herbal medicine with and promising efficacy. This herbal plant has been extensively cultivated in China. Currently, people usually rely on its morphological features to evalaute its pharmaceutical quality. In this study, laser micro-dissection system (LMD) was applied to isolate single fresh tissue of root of S. miltiorrhiza. Under fluorescent microscopic model, five tissues namely cork, cortex, phloem, xylem ray and vessel were well recognized and isolated accurately by LMD, respectively and then the distribution pattern of the major bioactive compounds in various tissues was investigated by ultra-performance liquid chromatography-quadrupole/time of flight-mass spectrometry, which aims to validate the traditional experience on evaluating pharmaceutical quality of Danshen by morphological features.ResultsTotal 62 chemical peak signals were captured and 58 compounds including 33 tanshinones, 23 salvianolic acids and 2 others were identified or tentatively characterized in micro-dissection tissues. Further semi-quantitative analysis indicated that the bioactive components such as tanshinones and salvianolic acids were mainly enriched in cork tissue.ConclusionIn the present study, analysis of metabolic profile in different tissues of roots of S. miltiorrhiza is reported for the first time. The distribution pattern of major bioactive components could enable medicinal vendors and consumers to relatively determine the pharmaceutical quality of Danshen by morphological features.Graphical abstractTissues-based chemical profiling of DanshenElectronic supplementary materialThe online version of this article (doi:10.1186/s13065-016-0187-7) contains supplementary material, which is available to authorized users.

BackgroundArdipusilloside-I (ADS-I) is a triterpenoid saponin extracted from Chinese medicinal herb Ardisiapusill A. DC. Previous studies have demonstrated the potent anti-tumor activities of ADS-I both in vitro and in vivo, and its main metabolites (M1 and M2) from human intestinal bacteria. However, the physicochemical properties and intestinal permeation rate of ADS-I and its metabolites are not understood. In this study, the octanol/water distribution coefficients (logP) of ADS-I and metabolites were investigated using standard shake flask technique, and their permeability properties was investigated across Caco-2 cells monolayer.ResultsThe logP of ADS-I, M1 and M2 was −0.01, 0.95 ± 0.04, 1.57 ± 0.11, respectively. The Papp values of ADS-I, M1 and M2 (in 10 μmol/L) across Caco-2 cell monolayers from the apical (AP) to basolateral (BL) direction were 1.88 ± 0.21 × 10−6 cm·s−1, 4.30 ± 0.43 × 10−6 cm·s−1, 4.74 ± 0.47 × 10−6 cm·s−1, respectively.ConclusionOur data indicated that ADS-I has the poorer intestinal absorption than its metabolites (M1 and M2) in these experimental systems, suggesting that the metabolites of ADS-I may be the predominant products absorbed by the intestine when ADS-I is administered orally.

BackgroundCyanoform is long known as one of the strongest acid. Cyanoform is only stable below −40 °C. The issue of the stability and tautomeric equilibria of cyanoform (CF) are investigated at the DFT and MP2 levels of theory. The present work presents a detailed study of structural tautomer interconversion in three different media, namely, in the gas phase, in a solvent continuum, and in a microhydrated environment where the first solvation layer is described explicitly by one or two water molecule. In all cases, the transition state has been localized and identified. Proton affinities, deprotonation energies and the Raman spectra are reported analyzed and discussed.ResultsThe 1 tautomer of cyanoform is shown to be more stable than 2 form by only 1.8 and 14.1 kcal/mol in the gas phase using B3LYP/6-311 ++G** and MP2/6-311 ++G** level of theory, respectively. This energy difference is reduced to 0.7 and 13.4 kcal/mol in water as a solvent using CPCM model using B3LYP/6-311 ++G** and MP2/6-311 ++G** level of theory, respectively. The potential energy barrier for this proton transfer process in the gas phase is 77.5 kcal/mol at MP2/6-311 ++G** level of theory. NBO analysis, analysis of the electrostatic potential (ESP) of the charge distribution, donor–acceptor interactions and charge transfer interactions in 1 and 2 are performed and discussed.ConclusionsGross solvent continuum effects have but negligible effect on this barrier. Inclusion of one and two water molecules to describe explicitly the first solvation layer, within the supermolecule model, lowers the barrier considerably (29.0 and 7.6 kcal/mol, respectively). Natural bond orbital (NBO) analysis indicated that the stability of the cyanoform arising from charge delocalization. A very good agreement between experimental and theoretical data has been found at MP2/6-311 ++G** for the energies. On other hand, B3LYP/6-311 ++G** level of theory has good agreement with experimental spectra for CF compound.Electronic supplementary materialThe online version of this article (doi:10.1186/s13065-016-0166-z) contains supplementary material, which is available to authorized users.

BackgroundVolatile organic compounds (VOCs) can be intermediates of metabolic pathways and their levels in biological samples may provide a better understanding about diseases in addition to potential methods for diagnosis. Headspace analysis of VOCs in urine samples using solid phase micro extraction (SPME) coupled to gas chromatography - mass spectrometry (GC-MS) is one of the most used techniques. However, it generally produces a limited profile of VOCs if applied to fresh urine. Sample preparation methods, such as addition of salt, base or acid, have been developed to improve the headspace-SPME-GC-MS analysis of VOCs in urine samples. These methods result in a richer profile of VOCs, however, they may also add potential contaminants to the urine samples, result in increased variability introduced by manually processing the samples and promote degradation of metabolites due to extreme pH levels. Here, we evaluated if freeze-drying can be considered an alternative sample preparation method for headspace-SPME-GC-MS analysis of urine samples.ResultsWe collected urine from three volunteers and compared the performances of freeze-drying, addition of acid (HCl), addition of base (NaOH), addition of salt (NaCl), fresh urine and frozen urine when identifying and quantifying metabolites in 4 ml samples. Freeze-drying and addition of acid produced a significantly higher number of VOCs identified than any other method, with freeze-drying covering a slightly higher number of chemical classes, showing an improved repeatability and reducing siloxane impurities.ConclusionIn this work we compared the performance of sample preparation methods for the SPME-GC-MS analysis of urine samples. To the best of our knowledge, this is the first study evaluating the potential of freeze-dry as an alternative sample preparation method. Our results indicate that freeze-drying has potential to be used as an alternative method for the SPME-GC-MS analysis of urine samples. Additional studies using internal standard, synthetic urine and calibration curves will allow a more precise quantification of metabolites and additional comparisons between methods.Graphical abstractEnhancing VOC profiling from urine samples.Electronic supplementary materialThe online version of this article (doi10.1186/s13065-016-0155-2) contains supplementary material, which is avaialble to authorize users.

BackgroundHelichrysum species are used extensively for stress-related ailments and as dressings for wounds normally encountered in circumcision rites, bruises, cuts and sores. It has been reported that Helichysum species are used to relief abdominal pain, heart burn, cough, cold, wounds, female sterility, menstrual pain.ResultsFrom the extracts of Helichrysum foetidum (L.) Moench, six known compounds were isolated and identified. They were 7, 4′-dihydroxy-5-methoxy-flavanone (1), 6′-methoxy-2′,4, 4′-trihydroxychalcone (2), 6′-methoxy-2′,4-dihydroxychalcone -4′-O-β-D-glucoside (3), apigenin (4), apigenin-7-O-β-D-glucoside (5), kaur-16-en-18-oic acid (6) while two known compounds 3,5,7-trihydroxy-8-methoxyflavone (12), 4,5-dicaffeoyl quinic acid (13) together with a mixture of phytosterol were isolated from the methanol extract of Helichrysum mechowianum Klatt. All the compounds were characterized by spectroscopic and mass spectrometric methods, and by comparison with literature data. Both extracts and all the isolates were screened for the protease inhibition, antibacterial and antifungal activities. In addition, the phytochemical profiles of both species were investigated by ESI-MS experiments.ConclusionsThese results showed that the protease inhibition assay of H. foetidum could be mainly attributed to the constituents of flavonoids glycosides (3, 5) while the compound (13) from H. mechowianum contributes to the stomach protecting effects. In addition, among the antibacterial and antifungal activities of all the isolates, compound (6) was found to possess a potent inhibitor effect against the tested microorganisms. The heterogeneity of the genus is also reflected in its phytochemical diversity. The differential bioactivities and determined constituents support the traditional use of the species. Molecular modelling was carried out by computing selected descriptors related to drug absorption, distribution, metabolism, excretion and toxicity (ADMET).Graphical abstractCompounds isolated from Helichrysum species (Compositae).Electronic supplementary materialThe online version of this article (doi:10.1186/s13065-015-0108-1) contains supplementary material, which is available to authorized users.

BackgroundBased on the pharmacological potency and structural features of succinimides, this study was designed to synthesize new ketoesters derivatives of succinimides. Furthermore, the synthesized compounds were evaluated for their possible anticholinesterase and antioxidant potentials. The compounds were synthesized by organocatalytic Michael additions of α-ketoesters to N-aryl maleimides. Acetyl and butyrylcholinesterase inhibitory activities were determined using Ellman’s spectrophotometric assay. The antioxidant activity was performed with DPPH and ABTS free radicals scavenging assay.ResultsThe Michael additions of α-ketoesters to maleimides was promoted by 8-hydroxyquinoline. The organocatalyst (8-hydroxyquinoline, 20 mol %) produced the compounds in relatively shorter time (20–24 h) and with excellent isolated yields (84-98 %). The synthesized compounds (1–4) showed outstanding acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory potentials, i.e., 98.75 and 90.00 % respectively for compound 2, with IC50 < 0.1 μg/mL. Additionally, compounds 1–4 revealed moderate antioxidant activity at different concentrations. In DPPH free radical scavenging assay, compound 1 showed dominant result with 72.41 ± 0.45, 52.49 ± 0.78 and 35.60 ± 0.75 % inhibition at concentrations of 1000, 500 and 250 μg/mL respectively, IC50 value of 440 μg/mL. However, the free radical scavenging was better when used ABTS free radicals. In ABTS free radicals scavenging assay compound 1 exhibited 88.51 ± 0.62 % inhibition at highest tested concentration i.e., 1000 μg/mL.ConclusionsHerein, we have synthesized four ketoesters derivatives of succinimides in a single step reaction and high yields. As a highlight, we have showed a first report on the anticholinesterase and antioxidant potentials of succinimides. All the compounds showed overwhelming enzyme inhibitions and moderate antioxidant potentials.Graphical Graphical representation of synthesis, anticholinesterase and antioxidant potentials of ketoester derivatives of succinimides.Electronic supplementary materialThe online version of this article (doi:10.1186/s13065-015-0107-2) contains supplementary material, which is available to authorized users.

BackgroundPurine nucleoside analogs (PNAs) constitute an important group of cytotoxic drugs for the treatment of neoplastic and autoimmune diseases. In the present study, classification models have been developed for the prediction of the anti-HIV activity of purine nucleoside analogs.ResultsThe topochemical version of superaugmented pendentic index-4 has been proposed and successfully utilized for the development of models. A total of 60 2D and 3D molecular descriptors (MDs) of diverse nature were selected for building the classification models using decision tree (DT), random forest (RF), support vector machine (SVM), and moving average analysis (MAA). The values of most of these descriptors for each of the analogs in the dataset were computed using the Dragon software (version 5.3). An in-house computer program was also employed to calculate additional MDs which were not included in the Dragon software. DT, RF, and SVM correctly classified the analogs into actives and inactives with an accuracy of 89 %, 83 %, and 78 %, respectively. MAA-based models predicted the anti-HIV activity of purine nucleoside analogs with a non-error rate up to 98 %. Therapeutic active spans of the suggested MAA-based models not only showed more potency but also exhibited enhanced safety as revealed by comparatively high values of selectivity index (SI). The statistical importance of the developed models was appraised via intercorrelation analysis, specificity, sensitivity, non-error rate, and Matthews correlation coefficient.ConclusionsHigh predictability of the proposed models clearly indicates an immense potential for developing lead molecules for potent but safe anti-HIV purine nucleoside analogs.

BackgroundFor a full understanding of the mechanical properties of a material, it is essential to understand the defect structures and associated properties and microhardness indentation is a technique that can aid this understanding.ResultsThe Vickers hardness on (010), {011} and {110} faces lay in the range of 304–363 MPa. The Knoop Hardnesses on the same faces lay in the range 314–482 MPa. From etching of three indented surfaces, the preferred slip planes have been identified as (001) and (101). For a dislocation glide, the most likely configuration for dislocation movement on the (001) planes is (001) [100] (|b| = 0.65 nm) and for the (101) plane as (101) left[10overline{1}right] (|b| = 1.084 nm) although (101) [010] (|b| = 1.105 nm) is possible. Tensile testing showed that at a stress value of 2.3 MPa primary twinning occurred and grew with increasing stress. When the stress was relaxed, the twins decreased in size, but did not disappear. The twinning shear strain was calculated to be 0.353 for the (101) twin plane.ConclusionsHMX is considered to be brittle, compared to other secondary explosives. Comparing HMX with a range of organic solids, the values for hardness numbers are similar to those of other brittle systems. Under the conditions developed beneath a pyramidal indenter, dislocation slip plays a major part in accommodating the local deformation stresses.Graphical abstractHMX undergoing tensile testing.Electronic supplementary materialThe online version of this article (doi:10.1186/s13065-015-0091-6) contains supplementary material, which is available to authorized users.

Background1,4-Diazepine derivatives are the seven membered, nitrogen containing heterocyclic ring systems possessing a wide range of therapeutic applications. 1,4-Diazepines attracted the attention of chemists and druggists due to their biological and medicinal properties, such as antimicrobial, anti-HIV and anticancer activities. Herein, we report the preparation, crystal structure determined by X-ray crystallographic methods and docking of the molecules with the potential target protein NS5B RNA polymerase.ResultsThe crystal structures and conformational studies of 1,4-diazepine [t-3, t-6-dimethyl-r-2,c-7-diphenyl-1,4-diazepan-5-one(DIAZ1)] and its nitroso derivative [t-3, t-6-dimethyl-1-nitroso-r-2,c-7-diphenyl-1,4-diazepan-5-one(DIAZ2)] are reported. The analyses of the molecules reveal that the seven membered diazepine ring systems adopt chair and boat conformations in compounds DIAZ1 & DIAZ2, respectively. In DIAZ2, the oxygen O2A is disordered over two positions with the refined occupancies of 0.792(7): 0.208(7) in the nitroso group. In both DIAZ1 & DIAZ2, the symmetry related molecules form a hetero/homo-dimer through N-H…O hydrogen bonds.ConclusionIn this study, the crystal structures of two new 1,4-diazepines, namely t-3, t-6-dimethyl-r-2,c-7-diphenyl-1,4-diazepan-5-one and t-3, t-6-dimethyl-1-nitroso-r-2,c-7-diphenyl-1,4-diazepan-5-one were synthesized and characterized by X-ray crystallographic methods. The docking studies show that the compounds inhibit at the active site of the target protein and can be utilized as potential drug molecules. In both the compounds, N-H…O hydrogen bonds lead to dimer formation. In DIAZ2, additionally a couple of C-H…O interactions are noted between the molecules.Graphical Structure and docking studies of 1,4-diazapine derivatives.Electronic supplementary materialThe online version of this article (doi:10.1186/s13065-015-0094-3) contains supplementary material, which is available to authorized users.

BackgroundDue to the lower health risks associated with the use of certain categories of smokeless tobacco products (STPs) such as Swedish snus, there is interest in the comparative levels of toxic chemical constituents in different types of STPs. A method has been developed and validated for the analysis of hydrazine in STPs. Seventy four commercial STPs from the US and Sweden, representing 80-90% of the 2010 market share for all the major STP categories in these two countries, as well as three reference STPs, were analysed for hydrazine.ResultsAqueous extracts of the STPs were treated with excess pentafluorobenzaldehyde (PFB), which reacted with hydrazine in solution to form decafluorobenzaldehyde azine (DFBA). DFBA was partitioned into hexane and then quantified by gas chromatography–mass spectrometry (GC–MS). The method was validated using five different types of STP, was linear in the range 8–170 ng/mL, and had limits of quantification (LOQ) from 26–53 ng of hydrazine per g of STP (as sold). The method was applied to the analysis of 74 contemporary STPs commercially available in the United States and Sweden, none of which were found to contain hydrazine above the LOQ or LOD. Trace levels of compounds showing chromatographic and mass spectral features consistent with hydrazine were identified at very low levels (sub-limit of detection, <10 ng/g) in the chromatograms of less than half of the 74 STPs examined; in contrast, for 40 of the STPs no evidence for the presence of hydrazine was observed. Where present, the levels of compounds consistent with hydrazine were estimated to be at least an order of magnitude lower than the only previous study to have quantified hydrazine in tobacco.ConclusionsOur results show that hydrazine is not a prevalent constituent of STPs, and when present is not quantifiable using currently available analytical methodology.