Compounds Of Interest Research Articles

Bee sensitivity derived from acute contact tests biased by standardised protocols?

In an acute contact test with bees the compound of interest is dissolved in a carrier solvent (frequently acetone) and then a droplet of the solution is placed on the dorsal thorax of the bee. The volume of the droplet is standardised to 1 µL for honeybees and to 2 µL for bumblebees. In practice the same droplet volume is used for bees with very different sizes. In this research the effect of the droplet volume was evaluated with acute contact tests with dimethoate for the alfalfa leafcutter bee, the red mason bee, the honeybee and the bumblebee. The results were analysed with a ToxicoKinetic ToxicoDynamic (TKTD) model to separate kinetic from dynamic effects. This allows to compare the sensitivity of the bee based on the effect threshold and not on the time, species and test dependent LD50s. The analysis of the test results indicates that the magnitude of the response of the bees increased with increasing droplet size. The results also showed that the manifestation of effects over time is slower for the red mason bee and the bumblebee compared to the honeybee and the alfalfa leafcutter bee. This implies that the result of a 2 day test with a fixed dosing volume results in different response for a bumblebee compared to the alfalfa leafcutter bee, not because of different sensitivities of the bees involved but due to the difference of relative dosed surface ratio. So comparing the sensitivity of bee species, based on standardised tests is biased and amplifies the sensitivity for the smaller bee species.

Dereplication of New Saponins from Agave bracteosa.

The genus Agave comprises over 400 species that are known for their diverse applications, which include being sources of fiber, food, and beverages. There has recently been increased interest in exploring the metabolic content of this genus, and in this respect, saponins are the main compounds of interest. Saponins for Agave bracteosa have not been described to date, and the current work addresses the dereplication of a saponin-rich fraction to identify the structures of six compounds. The dereplication methods involve the use of UPLC-MSE analysis, NMR spectroscopy and published data for Agave saponins. A green extraction and isolation provided ten pure saponins. Remarkably, nine of these saponins have not been reported previously, namely (25S)-cantalasaponin-1 and bractofuranosides A-H. These compounds were tested for cytotoxic activity. Bractofuranosides B (5) and G (10) displayed 57% and 53% cell viability on HeLa cells at 100 µM, respectively.

Supramolecular gels: a versatile crystallization toolbox.

Supramolecular gels are unique materials formed through the self-assembly of molecular building blocks, typically low molecular weight gelators (LMWGs), driven by non-covalent interactions. The process of crystallization within supramolecular gels has broadened the scope of the traditional gel-phase crystallization technique offering the possibility of obtaining crystals of higher quality and size. The broad structural diversity of LMWGs allows crystallization in multiple organic and aqueous solvents, favouring screening and optimization processes and the possibility to search for novel polymorphic forms. These supramolecular gels have been used for the crystallization of inorganic, small organic compounds of pharmaceutical interest, and proteins. Results have shown that these gels are not only able to produce crystals of high quality but also to influence polymorphism and physicochemical properties of the crystals, giving rise to crystals with potential new bio- and technological applications. Thus, understanding the principles of crystallization in supramolecular gels is essential for tailoring their properties and applications, ranging from drug delivery systems to composite crystals with tunable stability properties. In this review, we summarize the use of LMWG-based supramolecular gels as media to grow single crystals of a broad range of compounds.

Electro-sustainable Synthesis: Rapid and Efficient Production of Benzothiazole Derivatives through Electrochemical Means for Sustainable Chemistry

Abstract: Electro-organic synthesis suggested a mild, environmentally benign, and atom-efficient pathway to interesting and useful organic compounds. Organic electrochemistry offers an excellent alternative to conventional methods of organic synthesis, avoiding harsh, oxidizing and reducing agents, etc. In our reported work, electro-organic synthesis was carried out in an undivided cell at room temperature in the presence of lithium perchlorate as a supporting electrolyte. Electricity is utilized here instead of a chemical substance with a simple graphite-iron electrode combination. The generation of 2-substituted benzothiazoles was achieved through the amalgamation of bis(2- aminophenyl)disulfides with aromatic aldehydes under the influence of the electrodes. This synthetic process yielded a diverse array of 2-substituted benzothiazoles with satisfactory to excellent yields (64-91%). This is a gentle, sustainable, and metal-free condition for the synthesis of 2-substituted benzothiazoles. In this procedure, subsequent procedural steps encompassed the introduction of distilled water followed by filtration and drying processes to ensure the refinement of the final products.

A screen for cell envelope stress uncovers an inhibitor of prolipoprotein diacylglyceryl transferase, Lgt, in Escherichia coli

The increasing prevalence of antibiotic resistance demands the discovery of antibacterial chemical scaffolds with unique mechanisms of action. Phenotypic screening approaches, such as the use of reporters for bacterial cell stress, offer promise to identify compounds while providing strong hypotheses for follow-on mechanism of action studies. From a collection of ∼1,800 Escherichia coli GFP transcriptional reporter strains, we identified a reporter that is highly induced by cell envelope stress-pProm rcsA -GFP. After characterizing pProm rcsA -GFP induction, we assessed a collection of bioactive small molecules for reporter induction, identifying 24 compounds of interest. Spontaneous suppressors to one compound in particular, MAC-0452936, mapped to the gene encoding the essential prolipoprotein diacylglyceryl transferase, lgt. Lgt inhibition by MAC-0452936 inhibition was confirmed through genetic, phenotypic, and biochemical approaches. The oxime ester, MAC-0452936, represents a useful small molecule inhibitor of Lgt and highlights the potential of using pProm rcsA -GFP as a phenotypic screening tool.

Enhancement of Forskolin Production Using Aeroponic Cultivation of Coleus forskohlii and the Impact on the Plant Phytochemistry.

Accessing plant resources to extract compounds of interest can sometimes be challenging. To facilitate access and limit the environmental impact, innovative cultivation strategies can be developed. Forskolin is a molecule of high interest, mainly found in the roots of Coleus forskohlii. The aim of this study was to develop aeroponic cultivation methods to provide a local source of Coleus forskohlii and to study the impact of abiotic stress on forskolin and bioactive metabolite production. Three cultivation itineraries (LED lighting, biostimulant, and hydric stress) along with a control itinerary were established. The forskolin content in the plant roots was quantified using HPLC-ELSD, and the results showed that LED treatment proved to be the most promising, increasing root biomass and the total forskolin content recovered at the end of the cultivation period threefold (710.1 ± 21.3 mg vs. 229.9 ± 17.7 mg). Statistical analysis comparing the LED itinerary to the control itinerary identified stress-affected metabolites, showing that LEDs positively influence mainly the concentration of phenolic compounds in the roots and diterpenes in the aerial parts of Coleus forskohlii. Moreover, to better define the phytochemical composition of Coleus forskohlii cultivated in France using aeroponic cultivation, an untargeted metabolomic analysis was conducted using UHPLC-HRMS/MS analysis and molecular networks on both the root and aerial parts. This study demonstrates that aeroponic cultivation, especially with the application of an LED treatment, could be a very promising alternative for a local source of Coleus forskohlii leading to easy access to the roots and aerial parts rich in forskolin and other bioactive compounds.

Identification of a histone deacetylase inhibitor as a therapeutic candidate for congenital central hypoventilation syndrome

Congenital central hypoventilation syndrome (CCHS), a rare genetic disease caused by heterozygous PHOX2B mutations, ischaracterized by life-threatening breathing deficiencies. PHOX2B is a transcription factor required for the specification of the autonomic nervous system, which contains, in particular, brainstem respiratory centers. In CCHS, PHOX2B mutations lead to cytoplasmic PHOX2B protein aggregations, thus compromising its transcriptional capability. Currently, the only available treatment for CCHS is assisted mechanical ventilation. Therefore, identifying molecules with alleviating effects on CCHS-related breathing impairments is of primary importance. A transcriptomic analysis of cells transfected with different PHOX2B constructs was used to identify compounds of interest with the CMap tool. Using fluorescence microscopy and luciferase assay, the selected molecules were further tested invitro for their ability to restore the nuclear location and function of PHOX2B. Finally, an electrophysiological approach was used to investigate exvivo the effects ofthe most promising molecule on respiratory activities of PHOX2B-mutant mouse isolated brainstem. The histone deacetylase inhibitor SAHA was found to have low toxicity invitro, to restore the proper location and function of PHOX2B protein, and to improve respiratory rhythm-relatedparameters exvivo. Thus, our results identify SAHA as a promising agent to treat CCHS-associated breathing deficiencies.

Isolation of C-29 oxygenated oleanane triterpenoids and a (+)-muurolene type sesquiterpenoid from the fruiting bodies of Fuscoporia torulosa and their bioactivities.

Basidiomycetes with a wide variety of skeletons of secondary metabolites can be expected to be the source of new interesting biological compounds. During our research on basidiomycetes, two new C-29 oxygenated oleanane-type triterpenes (1 and 2) and torulosacid (3), a muurolene type sesquiterpenoid with a five-membered ether ring along with nine known compounds (4-12), were isolated from the MeOH extract of the fruiting bodies of Fuscoporia torulosa. The structures of 1-3 were determined by NMR and HREIMS analysis. Further studies on the stereochemistry of 3 were conducted using X-ray crystallographic analysis and comparison of experimental and calculated ECD spectra. In the antimicrobial assay of isolates, 1, 7, and 9 showed growth inhibitory activity against methicillin-resistant Staphylococcus aureus and other gram-positive strains. Isolation of oleanane type triterpenes from fungi including basidiomycetes, is a unique report that could lead to further isolation of new compounds and the discovery of unique biosynthetic enzymes.

Optimization of Polyphenol Extraction Conditions from Rhizomes of Curcuma zedoaria with Antioxidant, Anti-Inflammatory and Anti-Diabetic Activities In Vitro

The recovery of polyphenol compounds is seen as an arduous task because polyphenol compounds are available as free aglycones, as sugar or ester conjugates, or as polymers with several monomeric components. The response surface method (RSM) as a tool to optimize the factors that affect extraction efficacy as well as to obtain maximum recovery of the compounds of interest. This study optimizes ultrasound-assisted polyphenol extraction from Curcuma zedoaria rhizomes using response surface methodology (RSM). Three variables were considered: Ethanol concentration (70 - 90 %, v/v), temperature (60 - 80 °C), and ultrasound time (15 - 25 min). Data were analyzed by ANOVA, yielding an R2 of 0.9993, a significant interaction effect (p < 0.0001), and an insignificant lack-of-fit test (p = 0.6684). Optimal conditions for maximum polyphenol content (TPC = 31.05 ± 0.53 mg GAE/g powder) were 80.02 % ethanol, 68 °C, 20.47 min ultrasound time, and 1/10 (w/v) raw material/solvent ratio. Experimental values matched RSM predictions, confirming successful extraction optimization from Curcuma zedoaria rhizomes. The polyphenol-rich optimum extract from Curcuma zedoaria rhizomes has been studied for its antioxidant, anti-inflammatory and anti-inflammatory properties in vitro. The results were found, the optimum extract of Curcuma zedoaria rhizomes could perform effective neutralization activities of free radicals performed in DPPH test (IC50 = 5.89 ± 0.23 µg/mL), NO· (IC50 = 5.89 ± 0.23 µg/mL) and ABTS·+ (IC50 = 8.28 ± 0.12 µg/mL). Besides, this optimum extract had the ability to protect red blood cell membranes and inhibit protein denaturation due to heat with IC50 times values ​​such as 29.06 ± 0.35 and 30.24 ± 0.32 µg/mL. In addition, it also significantly inhibited α-amylase, α-glucosidase enzyme activities with IC50 values ​​of 5.89 ± 0.23 and 9.62 ± 0.11 μg/mL, respectively. This investigation showed that the polyphenol-rich optimum extract from Curcuma zedoaria rhizomes was a promising antioxidant, anti-inflammatory and anti-diabetic agent. HIGHLIGHTS Using ultrasound and the Box-Behnken design to extract polyphenols from Curcuma zedoaria rhizomes can speed up and improve extraction efficiency. The goal of this study is to maximize the extraction parameters for polyphenols from the rhizomes of Curcuma zedoaria. There is strong agreement between the experimental data and the model that predicts the polyphenol content in the Box-Behnken design. In vitro biological activities such as anti-inflammatory, antidiabetic and antioxidant properties are significantly correlated with polyphenol concentration. The findings of our investigation show a noteworthy enhancement in the bioavailability of polyphenol compounds through increased extraction efficiency and bioactivity. GRAPHICAL ABSTRACT

Political participation and financial education: Understanding personal and collective tradeoffs for a better citizenship

The paper documents a positive association between political participation, measured by the number of citizens voting at national elections, and awareness of the tradeoffs behind both private and public decisions that indicators of basic financial education can capture. The association is robust to the inclusion of a range of controls, stronger for the most difficult concepts of risk diversification and interest compounding, and consistent with the hypothesis that in countries where financial education is higher due to national cultural traits, voter turnout at national elections is higher.

Anomalous Nernst effect in the noncollinear antiferromagnet Mn5Si3

Investigating the off-diagonal components of the conductivity and thermoelectric tensor of materials hosting complex antiferromagnetic structures has become a viable method to reveal the effects of topology and chirality on the electronic transport in these systems. In this respect, Mn5Si3 is an interesting metallic compound that exhibits several antiferromagnetic phases below 100 K with different collinear and noncollinear arrangements of Mn magnetic moments determined from neutron scattering. Previous electronic transport measurements have shown that the transitions between the various phases give rise to large changes of the anomalous Hall effect. Here, we report measurements of the anomalous Nernst effect of Mn5Si3 single crystals that also show clear transitions between the different magnetic phases. In the noncollinear phase, we observe an unusual sign change of the zero-field Nernst signal with a concomitant decrease of the Hall signal and a gradual reduction of the remanent magnetization. Furthermore, a symmetry analysis of the proposed magnetic structures shows that both effects should actually vanish. These results indicate a symmetry-breaking modification of the magnetic state with a rearrangement of the magnetic moments at low temperatures, thus questioning the previously reported models for the noncollinear magnetic structure obtained from neutron scattering.

Unusually Large Ligand Field Splitting in Anionic Europium(III) Complexes Induced by a Small Imidazolic Counterion.

Luminescent trivalent lanthanide (Ln3+) complexes are compounds of technological interest due to their unique photophysical properties, particularly anionic tetrakis complexes, given their higher stability and emission quantum yields. However, structural studies on the cation-anion interaction in these complexes and the relation of such to luminescence are still lacking. Herein, the cation-anion interactions in two luminescent anionic tetrakis(2-thenoyltrifluoroacetonato)europate(III) complexes with alkylimidazolium cations, specifically 1-ethyl-3-methylimidazolium and 1-butyl-3-methylimidazolium are investigated. The Eu3+ complexes were synthesized and characterized by elemental analysis, mass spectrometry, and single-crystal X-ray crystallography, and their luminescence spectra were recorded at 77 K. Quantum chemical calculations were also performed. X-ray crystallography revealed hydrogen bonds between the enolate ligands and imidazolium ring hydrogens. The 1-butyl-3-methylimidazolium complex had two crystallographic Eu3+ sites, also confirmed by luminescence spectroscopy. The 1-ethyl-3-methylimidazolium complex exhibited an unusual 300 cm-1 splitting in the 5D0 → 7F1 transition, as reproduced by ligand field calculations, suggesting a stronger hydrogen bonding due to the smaller substituent. We hypothesize that this strong bonding likely causes angular distortions, resulting in high ligand field splittings.

Synthesis of Samarium Nitride Thin Films on Magnesium Oxide (001) Substrates Using Molecular Beam Epitaxy

Rare-earth nitrides are an exciting family of materials with a wide variety of properties desirable for new physics and applications in spintronics and superconducting devices. Among them, samarium nitride is an interesting compound reported to have ferromagnetic behavior coupled with the potential existence of p-wave superconductivity. Synthesis of high-quality thin films is essential in order to manifest these behaviors and understand the impact that vacancies, structural distortions, and doping can have on these properties. In this study, we report the synthesis of samarium nitride monocrystalline thin films on magnesium oxide (001) substrates with a chromium nitride capping layer using molecular beam epitaxy (MBE). We observed a high-quality monocrystalline SmN film with matching orientation to the substrate, then optimized the growth temperature. Despite the initial 2 nm of growth showing formation of a potential samarium oxide layer, the subsequent layers showed high-quality SmN, with semiconducting behavior revealed by an increase in resistivity with decreasing temperature. These promising results highlight the importance of studying diverse heteroepitaxial schemes and open the door for integration of rare-earth nitrides and transition metal nitrides for future spintronic devices.

Principles and challenges of whole cell microbial biosensors in the food industry.

Whole cell microbial biosensors (WCMB) are mostly genetically modified microorganisms used to detect target molecules as indicators of biological and chemical contaminants as well as in the identification of compounds of interest in the food industry. The specificity and sensitivity of these biosensors are achieved through the design of genetic circuits that make use of genetic sequences such as promoters, terminators, genes encoding regulatory proteins or reporter proteins, among others. Despite the advances of WCMBs for their application, significant challenges are faced, such as cell stability, regulatory restrictions, and the need to optimize response times so that they can be a competitive detection tool in the market. This review explores the technological progress, potential and limitations of WCMBs in the food industry, starting by reviewing the operating principles of biosensors. The importance of selecting appropriate chassis cells and the integration of recognition elements and transducers to maximize their effectiveness in the detection of contaminants and compounds of interest in the food industry is highlighted.

Synthesis of pyrazole and 1,3,4-oxadiazole derivatives of pharmaceutical potential

Heterocyclic compounds are important molecules that serve as scaffolds or linkers for the core structure of numerous drug substances. In particular, pyrazole and 1,3,4-oxadiazole are compounds of great interest due to their comprehensive biological activities and interesting structural features. Here, we described an efficient and economical synthetic route leading to N-phenyl substituted pyrazole and 1,3,4-oxadiazole derivatives. Retrosynthetic disconnective analysis showed that the N-phenyl substituted pyrazole can be obtained from chalcone, accessible from the respective aldehyde, and acetophenone. The disubstituted 1,3,4-oxadiazole can be constructed from the respective aldehyde, which originates from pyrrole-containing compound, and formyl chloride. Based on our retrosynthetic analysis, N-phenyl substituted pyrazole was obtained by cyclization of the respective chalcone with phenylhydrazine to give pyrazoline which was in turn converted into pyrazole by oxidative aromatization. Potassium carbonate and a catalytic amount of molecular iodine were used to oxidatively cyclize semicarbazones into 1,3,4-oxadiazoles in a transition metal-free process. Novel pyrazole and 1,3,4-oxadiazoles with potential biological activity are investigated as antituberculosis, anticonvulsant, antidiabetic, anticancer, and tyrosinase inhibitory agents.

Antioxidant activity of Zuccagnia-type propolis: A combined approach based on LC-HRMS analysis of bioanalytical-guided fractions and computational investigation

This study reports a combined approach to assess the antioxidant activity of Zuccagnia-type propolis. Fractions exhibiting the highest antioxidant activities evidenced by DPPH, a β-carotene bleaching and superoxide radical scavenging activity-non-enzymatic assays, were processed by LC-HRMS/MS to characterize the relevant chemical compounds. A computational protocol based on the DFT calculations was used to rationalize the main outcomes. Among the 28 identified flavonoids, caffeic acids derivatives were in the fraction exhibiting the highest antioxidant activity, with 1-methyl-3-(4′-hydroxyphenyl)-propyl caffeic acid ester and 1-methyl-3-(3′,4′-dihydroxyphenyl)-propyl caffeic acid ester as major components. Results clearly showed roles of specific chemical motifs, which can be supported by the computational analysis.This is the first report ascribing the antioxidant ability of Zuccagnia-type propolis to its content in specific caffeic acid derivatives, a potential source of radical scavenging phytochemicals. The proposed protocol can be extended to the study of other plant-products to address the most interesting bioactive compounds.

Excess copper promotes an increase in the concentration of metabolites in Tridax procumbens L.

The study investigated the effects of cultivating Tridax procumbens in hydroponic conditions with different concentrations of copper ions, aiming to understand the physiological changes and the impact on the biosynthesis of secondary metabolites. The treatments consisted of a completely randomized design, with five increasing concentrations of copper (T0 = 0.235, T1 = 12.5, T2 = 25, T3 = 50, T4 = 100µmol L-1 of Cu), under controlled conditions for 36days. Analysis of bioactive compounds in leaves was performed by HPLC-DAD and ESI-MS. Several phenolic compounds, alkaloids, phytosterols and triterpenoids were identified, demonstrating the plant's metabolic plasticity. The highest dose of copper (100µmol L-1) significantly promoted voacangine, the most predominant compound in the analyses. Notably, 66.7% of the metabolites that showed an increase in concentration, were phenolic compounds. Furthermore, treatments with 12.5 and 25µmol L-1 of copper were identified as promoting the biosynthesis of phytosterols and triterpenoids. These biochemical adaptations can play a fundamental role in the survival and development of plants in environments contaminated by metals, and from this it is possible to determine cultivation techniques that maximize the biosynthesis of the compound of interest.

Developing and Testing Standards to Assess Atmospheric Corrosion of Silver Witness Coupons

Silver witness coupons are used to assess the corrosivity and chemistry of an ambient environment. The formation of silver corrosion products such as silver chloride is highly dependent on local conditions. However, the mechanisms that are responsible for these corrosion products are not well-understood, and there is a lack of standards used to compare and assess the quality of observations.The goal of this study is to synthesize silver corrosion film standards with known thickness and morphology. Compounds of interest include silver chloride, silver oxide, silver sulfide, silver sulfite, and silver sulfate. These compounds were generated electrochemically by oxidizing the silver in the presence of the anion of interest (chloride, sulfite, or sulfate), chemically by submerging the silver in a solution containing the anion, and chemically by dipping the silver in molten silver salts. The surface chemistry of these films was then analyzed using galvanostatic reduction, x-ray diffraction, x-ray photon spectroscopy, Raman spectroscopy, and energy dispersion spectroscopy. The films generated from each method were compared against each other to determine the optimal film thickness and morphology. In the future, these results will be compared against the surface chemistry of silver films formed by testing in laboratory chambers or by exposure in field environments. Figure 1

Evaluation of reinforcement learning in transformer-based molecular design

Designing compounds with a range of desirable properties is a fundamental challenge in drug discovery. In pre-clinical early drug discovery, novel compounds are often designed based on an already existing promising starting compound through structural modifications for further property optimization. Recently, transformer-based deep learning models have been explored for the task of molecular optimization by training on pairs of similar molecules. This provides a starting point for generating similar molecules to a given input molecule, but has limited flexibility regarding user-defined property profiles. Here, we evaluate the effect of reinforcement learning on transformer-based molecular generative models. The generative model can be considered as a pre-trained model with knowledge of the chemical space close to an input compound, while reinforcement learning can be viewed as a tuning phase, steering the model towards chemical space with user-specific desirable properties. The evaluation of two distinct tasks—molecular optimization and scaffold discovery—suggest that reinforcement learning could guide the transformer-based generative model towards the generation of more compounds of interest. Additionally, the impact of pre-trained models, learning steps and learning rates are investigated.Scientific contributionOur study investigates the effect of reinforcement learning on a transformer-based generative model initially trained for generating molecules similar to starting molecules. The reinforcement learning framework is applied to facilitate multiparameter optimisation of starting molecules. This approach allows for more flexibility for optimizing user-specific property profiles and helps finding more ideas of interest.

Residues of veterinary drugs and heavy metal contamination in livestock and poultry meat from Hunan Province, China

ABSTRACT Livestock and poultry meat consumption play an important role in the dietary structure of Chinese residents. However, the extent of residues of veterinary drugs and heavy metal contamination in livestock and poultry meat and their by-products within Hunan province is not extensively studied. This survey aimed to fill this gap by assessing the presence of 76 veterinary drug residues in Hunan province. Additionally, heavy metals in pork and pig liver were also assessed. The obtained findings suggest that residues of veterinary drugs are still present in livestock and poultry meat, as well as their by-products, within Hunan province. However, the contamination of heavy metals remained within the food safety limits. These results underscore the significance of establishing more refined criteria for assessing human exposure, taking into account factors such as consumption patterns, product varieties and chemical compounds of interest.