In vitro anticancer and antibacterial potentials of selected medicinal plants and isolation and characterization of a natural compound from Withania coagulans

In the current study, five different plants, Syzygium Cumini, Fagonia cretica, Acacia modesta, Withania coagulans, and Olea europaea aqueous extracts were prepared and applied against the anticancer and antibacterial activities. It was observed that O. Europaea extract shows the highest anticancer activity with cell viability of 21.5%. All the five plants extract was also used against the inhibition of Bacillus subtilis where O. Europaea extract shows a promising inhibitory activity of 3.2 cm followed by W. coagulans. Furthermore, W. coagulans was subjected to the process of column chromatography as a result a withanolide was isolated. The fast atom bombardment mass spectrometry (FAB-MS) and high resolution fast atom bombardment (HRFAB-MS) [M + 1] indicated molecular weight at m/z 453 and molecular formula C28H37O5. The UV–Vis. spectrum shows absorbance at 210 nm suggesting the presence of conjugated system, and Fourier-transform infrared spectroscopy (FTIR) was recorded to explore the functional groups. Similarly, 1D and 2D NMR spectroscopy techniques such as 1H, 13C NMR, correlation spectroscopy (COSY-45°), heteronuclear single quantum correlation (HSQC), heteronuclear multiple bond correlation (HMBC) and Nuclear Overhauser effect Spectroscopy (NOESY) techniques was carried out to determine the unknown natural product. The collective data of all these techniques established the structure of the unknown compound and recognized as a withanolide.

Molecular descriptors – an useful tool for assessing the physico-chemical properties of hallucinogenic drugs of abuse

Molecular descriptors play a fundamental role in chemistry and pharmaceutical sciences, being defined as a way to transform molecules into a set of numbers, allowing the mathematical assessment of the chemical information characterizing a molecule. This study presents the usefulness of molecular descriptors for the determination of physico-chemical properties of a series of new hallucinogenic amphetamines. Molecular descriptors of these compounds was performed with the Dragon 5.5 software. The chemometric processing of the information allowed the determination of structural correlations (similarities) between this class of designer drugs and an unknown compound.

Investigations on the Degradation of the Bile Salt Cholate via the 9,10-Seco-Pathway Reveals the Formation of a Novel Recalcitrant Steroid Compound by a Side Reaction in Sphingobium sp. Strain Chol11

Bile salts such as cholate are steroid compounds from the digestive tracts of vertebrates, which enter the environment upon excretion, e.g., in manure. Environmental bacteria degrade bile salts aerobically via two pathway variants involving intermediates with Δ1,4- or Δ4,6-3-keto-structures of the steroid skeleton. Recent studies indicated that degradation of bile salts via Δ4,6-3-keto intermediates in Sphingobium sp. strain Chol11 proceeds via 9,10-seco cleavage of the steroid skeleton. For further elucidation, the presumptive product of this cleavage, 3,12β-dihydroxy-9,10-seco-androsta-1,3,5(10),6-tetraene-9,17-dione (DHSATD), was provided to strain Chol11 in a co-culture approach with Pseudomonas stutzeri Chol1 and as purified substrate. Strain Chol11 converted DHSATD to the so far unknown compound 4-methyl-3-deoxy-1,9,12-trihydroxyestra-1,3,5(10)7-tetraene-6,17-dione (MDTETD), presumably in a side reaction involving an unusual ring closure. MDTETD was neither degraded by strains Chol1 and Chol11 nor in enrichment cultures. Functional transcriptome profiling of zebrafish embryos after exposure to MDTETD identified a significant overrepresentation of genes linked to hormone responses. In both pathway variants, steroid degradation intermediates transiently accumulate in supernatants of laboratory cultures. Soil slurry experiments indicated that bacteria using both pathway variants were active and also released their respective intermediates into the environment. This instance could enable the formation of recalcitrant steroid metabolites by interspecies cross-feeding in agricultural soils.

Formulas of Compounds and Percent Composition

Formulas of Compounds and Percent Composition describe the percent composition of compounds in terms of the number of constituent atoms and their masses. The empirical formula is presented as a way of obtaining the chemical formula of an unknown compound from analytical data. Further discussion shows the relation of molecular formula to empirical formula and molar mass.

Biclique extension as an effective approach to predict novel interaction partners in metabolic compound-protein interaction networks.

Motivation: Metabolic networks are complex systems of connected chemical reactions with physical interactions between metabolites and proteins playing a critical role for both metabolic conversion and regulation. In this study, we aimed to predict previously unknown compound-protein interactions (CPI) by transferring the concept of biclique extension, which was developed in the context of drug-target interaction prediction and that is based on the rationale that interactions that readily extend an existing biclique are real, to metabolic CPI networks. Results: We developed and tested a workflow to predict CPIs based on the concept of extending existing bicliques and applied it to E. coli and human using their respective known CPI network as input. Depending on the chosen biclique size, for the E. coli network we reached a sensitivity of 39% with an associated precision of 59%. For the larger human CPI network, a sensitivity of 78% with a false-positive rate of less than 5% and an associated precision of 75% was obtained. At more stringent settings, a precision as high as 95% was attainable at the expense of a lowered recall. Prediction performance significantly exceeded that obtained using randomized networks as input. Predicted novel interactions were tested for biomolecular function involvement, with TCA-cycle and ribosomal processes found associated with particularly pronounced statistical significance. As we demonstrate, our approach holds great potential to increase efficiency of experimental testing of CPIs and can readily be transferred to other species of interest. Availability and implementation: The R code and datasets are available at https://github.com/SandraThieme/BiPredict.

Bacterial Enrichment Cultures Biotransform the Mycotoxin Deoxynivalenol into a Novel Metabolite Toxic to Plant and Porcine Cells

The mycotoxin deoxynivalenol (DON), produced in wheat, barley and maize by Fusarium graminearum and Fusarium culmorum, is threatening the health of humans and animals. With its worldwide high incidence in food and feed, mitigation strategies are needed to detoxify DON, maintaining the nutritional value and palatability of decontaminated commodities. A promising technique is biological degradation, where microorganisms are used to biotransform mycotoxins into less toxic metabolites. In this study, bacterial enrichment cultures were screened for their DON detoxification potential, where DON and its potential derivatives were monitored. The residual phytotoxicity was determined through a bioassay using the aquatic plant Lemna minor L. Two bacterial enrichment cultures were found to biotransform DON into a still highly toxic metabolite for plants. Furthermore, a cytotoxic effect was observed on the cellular viability of intestinal porcine epithelial cells. Through liquid chromatography high-resolution mass spectrometry analysis, an unknown compound was detected, and tentatively characterized with a molecular weight of 30.0 Da (i.e., CH2O) higher than DON. Metabarcoding of the subsequently enriched bacterial communities revealed a shift towards the genera Sphingopyxis, Pseudoxanthomonas, Ochrobactrum and Pseudarthrobacter. This work describes the discovery of a novel bacterial DON-derived metabolite, toxic to plant and porcine cells.

N,N-Bis(Hexyl α-d-Acetylmannosyl) Acrylamide

Glycosyl monomers for the assembly of multivalent ligands are typically synthesized using carbohydrates with biological functions and polymerizable functional groups such as acrylamide or styrene introduced into the carbohydrate aglycon, and monomers polymerized using a radical initiator. Herein, we report the acryloylation of 6-aminohexyl α-mannoside and its conversion into the glycosyl monomer bearing an acrylamide group. The general acryloylation procedure afforded the desired N-hexyl acetylmannosyl acrylamide monomer as well as an unexpected compound with a close Rf value. The compounds were separated and analyzed by nuclear magnetic resonance spectroscopy and mass spectrometry, which revealed the unknown compound to be the bivalent N,N-bis(hexyl α-d-acetylmannosyl) acrylamide monomer, which contains two hexyl mannose units and one acrylamide group. To the best of our knowledge, this side reaction has not previously been disclosed, and may be useful for the construction of multivalent sugar ligands.

Stability of Compounded Clozapine 25 mg/mL and 50 mg/mL Suspensions in Plastic Bottles

Background: Clozapine oral suspension is not commercially available in Canada but is required for administration to patients who cannot swallow intact tablets. Objective: To evaluate the stability of 25 mg/mL and 50 mg/mL clozapine suspensions prepared in a 50:50 mixture of methylcellulose gel 1% and Oral Syrup (flavoured syrup vehicle, Medisca Pharmaceutique Inc) and stored in amber glycol-modified polyethylene terephthalate (PET-G) bottles over 120 days at 4°C and 25°C. Methods: This study used a validated reverse-phase stability-indicating liquid chromatographic method capable of quantifying clozapine, 3 known degradation compounds, a known impurity, and an unknown compound. Three separate batches of 25 mg/mL and 50 mg/mL clozapine suspensions were prepared, divided into 100-mL aliquots, and stored in 120-mL PET-G bottles. Half of the bottles from each concentration were stored at room temperature (20°C to 25°C) and the other half were stored in the refrigerator (2°C to 8°C). On study days 0, 28, 60, 90, and 120, concentrations of clozapine, each of the 3 known clozapine degradation products, a known impurity, and an unknown compound were determined. Results: When suspensions were stored in PET-G containers at room temperature or under refrigeration for 120 days, the concentration of clozapine remained above 95% of initial concentration, and the measured concentration of degradation products and impurities did not exceed the 0.5% limits set by regulatory authorities worldwide. The proportion of the initial concentration of clozapine remaining on day 120, based on fastest degradation rate with 95% confidence (1-sided), exceeded 92%, and the only degradation product found (clozapine lactam, 0.2%) and an unknown impurity (0.2%) also did not exceed allowable limits. Conclusions: Compounded clozapine suspensions of 25 mg/mL and 50 mg/mL can be stored in amber PET-G containers for up to 120 days after preparation with storage at room temperature or under refrigeration. RÉSUMÉ Contexte : La clozapine en suspension orale n’est pas disponible sur le marché canadien, mais elle est nécessaire pour les patients qui ne peuvent l’avaler sous forme de comprimé intact. Objectif : Évaluer la stabilité des suspensions de clozapine de 25 mg/mL et de 50 mg/mL, préparées dans un mélange 50:50 de gel méthylcellulose à 1 % et de Sirop Oral (véhicule de sirop aromatisé, MEDISCA) et conservées dans des flacons ambrés en polytéréphtalate d’éthylène modifié au glycol (PET-G) pendant 120 jours à des températures de 4°C et 25°C. Méthode : Cette étude a utilisé une méthode validée par chromatographie liquide indicatrice de stabilité en phase inverse pouvant quantifier la clozapine, trois composés de dégradation connus, une impureté connue et un composé inconnu. Trois lots séparés de suspensions de clozapine de 25 mg/mL et de 50 mg/mL ont été préparés, divisés dans des aliquotes de 100-mL et stockés dans des flacons en PET-G de 120-mL. La moitié des flacons de chaque concentration a été conservée à température ambiante (de 20°C à 25°C), et l’autre moitié au réfrigérateur (de 2°C à 8°C). Aux jours 0, 28, 60, 90 et 120 de l’étude, on a déterminé les concentrations de clozapine, celles de chacun des trois produits de dégradation de la clozapine, celles d’une impureté connue et d’un complexe inconnu. Résultats : Lorsque les suspensions étaient stockées dans des contenants en PET-G à température ambiante et réfrigérées pendant 120 jours, la concentration de clozapine demeurait au-dessus de 95 % de la concentration initiale; la concentration mesurée des produits de dégradation et des impuretés ne dépassait pas la limite de 0,5 % fixée par les autorités de règlementation mondiales. La proportion de concentration initiale de clozapine restante au 120e jour, sur la base du taux de dégradation le plus rapide avec un intervalle de confiance de 95 % (unilatéral), dépassait 92 %, et le seul produit de dégradation trouvé (clozapine lactam, 0,2 %) ainsi qu’une impureté inconnue (0,2 %) ne dépassaient pas non plus les limites autorisées. Conclusions : Les suspensions de clozapine composées de 25 mg/mL et de 50 mg/mL peuvent être conservées dans des contenants ambrés PET-G jusqu’à 120 jours après leur préparation, soit à température ambiante, soit dans un réfrigérateur.

Bank vole alarm pheromone chemistry and effects in the field

Chemical communication plays an important role in mammalian life history decisions. Animals send and receive information based on body odour secretions. Odour cues provide important social information on identity, kinship, sex, group membership or genetic quality. Recent findings show, that rodents alarm their conspecifics with danger-dependent body odours after encountering a predator. In this study, we aim to identify the chemistry of alarm pheromones (AP) in the bank vole, a common boreal rodent. Furthermore, the vole foraging efficiency under perceived fear was measured in a set of field experiments in large outdoor enclosures. During the analysis of bank vole odour by gas chromatography–mass spectrometry, we identified that 1-octanol, 2-octanone, and one unknown compound as the most likely candidates to function as alarm signals. These compounds were independent of the vole’s sex. In a field experiment, voles were foraging less, i.e. they were more afraid in the AP odour foraging trays during the first day, as the odour was fresh, than in the second day. This verified the short lasting effect of volatile APs. Our results clarified the chemistry of alarming body odour compounds in mammals, and enhanced our understanding of the ecological role of AP and chemical communication in mammals.