Chemical Classes Research Articles

Seasonal and circadian rhythms of clerodane diterpenes and glycosylated flavonoids in two varieties of Casearia sylvestris Sw. (Salicaceae)

Casearia sylvestris Sw. (Salicaceae) is noted for its morphological and chemical plasticity and pharmacological properties. The present study investigates two of its varieties: C. sylvestris var. sylvestris, predominant in dense and humid forests and ecotones and characterized by clerodane diterpenes; and C. sylvestris var. lingua, mainly found in xeric and open savannah areas and containing phenolic compounds. Despite their comprehensive chemical profiles, the dynamics of clerodane diterpenes and glycosylated flavonoids remain unknown. This study thus aimed to describe seasonal and circadian variations in their content in the leaves of the two varieties. The relative contents of five diterpenes and three glycosylated flavonoids were monitored monthly, every 3 h for 48 h, over 1 year via high-performance liquid chromatography coupled to diode array detection (HPLC-UV-DAD). The differential expression of photosynthetic proteins (Rubisco and photosystem II) was analyzed by Western blotting. The contents of both chemical classes decreased during the reproductive stage, though the prevalence of diterpenes in var. sylvestris and flavonoids in var. lingua remained unchanged; furthermore, even when the plants are grown under the same geographic and environmental conditions, Rubisco expression in var. lingua is twice that of var. sylvestris. In var. lingua, photosystem II proteins are 10% less expressed. The study reveals the circadian and seasonal fluctuations and, thus, prevalence of the two main compound classes in the examined varieties. The expression of the investigated photosynthetic proteins provides insights into the two varieties, supporting the prevalence of var. lingua in Cerrado areas and var. sylvestris in Atlantic Forest areas.

Identification and hazard prioritization of hydrophobic organic chemicals in flowback and produced water particles: Implications for water management

Hydraulic fracturing flowback and produced water (HF-FPW) has raised significant concerns owing to its potential impact on aquatic organisms and human health. Understanding the chemical composition of HF-FPW is crucial for developing appropriate management and remediation strategies. Herein, we performed nontarget screening of hydrophobic organic chemicals in the particulate phase of FPW (P-FPW) using gas chromatography-Orbitrap mass spectrometry coupled with cheminformatic analysis. In total, 5807 features were discovered, with 209 annotated with positive confidence levels, which were further classified based on their chemical taxonomy and functional use information. We found that benzenoids dominated the chemical class, followed by hydrocarbons. The annotated chemicals were classified into fragrances, catalysts, antimicrobials, antioxidants, and other classes. Chemical overlap across countries (China vs. Canada) and wells was observed, with most chemicals reaching peak intensity within 24 or 48 h after the initial flowback and gradually decreasing. Approximately two-thirds of the identified or annotated chemicals have not been previously reported or included in existing HF-related databases, indicating expanded chemical coverage by the current screening workflow. A Toxicological Priority Index (ToxPi) scheme, which integrates chemical properties, ecological toxicities, and in vivo exposure potentials, was adopted to prioritize chemicals for further evaluation. Seven chemicals were proposed as prioritized compounds, of which the ester derivative of perfluorobutanoic acid, octacosyl heptafluorobutyrate (confidence level 2), exhibited the highest ToxPi score. Notably, most prioritized substances have limited toxicological data and are beyond the routine monitoring of the HF industry, highlighting significant gaps in our understanding of HF-related chemical content and environmental risk associated with water management.

Integrative LC-MS and GC-MS metabolic profiling unveils dynamic changes during barley malting

Malting involves complex biochemical transformations affecting sensory and quality attributes. Despite extensive research on storage carbohydrates and proteins in malting, the lack of a detailed metabolic understanding of this process limits our ability to assess and enhance malt quality. This study employed untargeted GC-MS and LC-MS metabolite profiling across six malting timepoints to identify 4980 known metabolites, 82 % of which exhibited significant changes during the malting process. Here we identified stage-dependent metabolic shifts and dynamic chemical classes and pathways between each studied stage. These results can guide the fine-tuning of malting conditions to improve malt quality for beer production and other malt-based applications. Additionally, metabolites with antimicrobial properties were identified, underscoring the interplay between barley and microbial metabolic processes during malting. Further research into these microbial metabolites and cognate microbes may lead to novel malting assessment traits for high-quality and safe malted barley.

Development of an advanced analytical technique for detecting multiple pesticide residues in vegetables through liquid chromatography tandem mass spectroscopy (LC-MS/MS)

A comprehensive LC-MS/MS method, which employs Positive Electrospray Ionization (PEI) and Multiple Reaction Monitoring (MRM) was developed for the simultaneous determination of 35 pesticides belonging to various chemical classes in tomato, brinjal, chili, and okra samples. Extraction was facilitated using a modified QuEChERS method, which allows efficient sample analysis in a single run. Calibration curves for each pesticide exhibited linearity within the concentration range of 0.0025 to 0.1 µg mL−1, with correlation coefficients ranging from 0.993 to 0.999. Mean recoveries at five fortification levels (0.01 to 0.5 µg kg−1) ranged from 80 to 90%, demonstrating satisfactory precision (RSD < 20%). The matrix effects, mitigated through an optimized cleanup process, were observed within the range of 6.42% to 19.52%. The developed method having the limit of quantification of 0.01 mg kg−1 for all 35 pesticides, proved to be highly sensitive and rapid for multi-residue estimation in diverse vegetable samples. Subsequently, the method was used to analyze the market samples from Varanasi, India, which revealed the presence of pesticides like Chlorpyrifos, Chlorantraniliproleand Indoxacarb in tomato, brinjal, chili and okra. Therefore, the method could be considered as a robust tool for monitoring pesticide residues in vegetables, aiding in quality assessment and regulatory compliance in the agriculture sector.

Comprehensive characterization of volatile compounds in Iranian black teas using chemometric analysis of GC-MS fingerprints

Black tea, a widely popular non-alcoholic beverage, is renowned for its unique aroma and has attracted significant attention due to its complex composition. However, the chemical profile of Iranian tea remains largely unexplored. In this research, black tea samples from key tea cultivation regions in four geographical areas in northern Iran were firstly analyzed using headspace solid-phase microextraction followed by gas chromatography–mass spectrometry (HS-SPME-GC–MS) to separate, identify, and quantify their volatile organic compounds. Subsequently, employing a robust investigative strategy, we utilized for the first time the well-known multivariate curve resolution-alternating least square (MCR-ALS) method as a deconvolution technique to analyze the complex GC–MS peak clusters of tea samples. This approach effectively addressed challenges such as severe baseline drifts, overlapping peaks, and background noise, enabling the identification of minor components responsible for the distinct flavors and tastes across various samples. The MCR-ALS technique significantly improved the resolution of spectral and elution profiles, enabling both qualitative and semi-quantitative analysis of tea constituents. Qualitative analysis involved comparing resolved peak profiles to theoretical spectra, along with retention indices, while semi-quantification was conducted using the overall volume integration (OVI) approach for volatile compounds, providing a more accurate correlation between peak areas and concentrations. The application of chemometric tools in GC–MS analysis increased the number of recognized components in four tea samples, expanding from 54 to 256 components, all with concentrations exceeding 0.1 %. Among them, 32 volatile compounds were present in every tea sample. Hydrocarbons (including alkenes, alkanes, cycloalkanes, monoterpenes and sesquiterpenes), esters and alcohols were the three major chemical classes, comprising 78 % of the total relative content of volatile compounds. Analyzing black teas from four distinct regions revealed variations not only in their volatile components but also in their relative proportions. This integrated approach provides a comprehensive understanding of the volatile chemical profiles in Iranian black teas, enhances knowledge about their unique characteristics across diverse geographical origin, and lays the groundwork for quality improvement.

Evaluation of a New In Chemico Skin Corrosion Test

The purpose of this study is to evaluate a novel macromolecular test method for the identification of dermal corrosives. The simple in chemico test procedure involves allowing the material to be tested to interact with a skin biomarker for corrosivity and then adding a detection reagent. The corrosivity of the test substance is predicted based on the measured macromolecular damage, which results in reduced optical density of the detection reagent as compared with controls. This study aims to determine if such an extremely simple, cell-free test method can accurately identify dermal corrosives. To determine predictivity and repeatability, we tested 60 chemicals (30 in vivo dermal corrosives and 30 in vivo dermal noncorrosives; all tested in triplicate) representative of a broad range of chemical classes, functional groups, mixtures, and levels of toxicity. Validation results indicate the GHS multicategory and packing group assignment accuracy is on par with that of the Reconstructed Human Epidermis test method and the Membrane Barrier test method and for the global identification of corrosives, the method has a considerably higher accuracy (98 % vs. ∼80 %).

Multi- and poly-pharmacology of carbonic anhydrase inhibitors.

Eight genetically distinct families of the enzyme carbonic anhydrase (CA, EC 4.2.1.1) were described in organisms allover the phylogenetic tree. They catalyze the hydration of CO2 to bicarbonate and protons, and are involved in pH regulation, chemosensing and metabolism. The 15 α-CA isoforms present in humans are pharmacological drug targets known for decades, their inhibitors being used as diuretics, antiglaucoma, antiepileptic or antiobesity drugs, as well as for the management of acute mountain sickness, idiopathic intracranial hypertension and recently, as antitumor theragnostic agents. Other potential applications include the use of CA inhibitors (CAIs) in inflammatory conditions, cerebral ischemia, neuropathic pain, or for Alzheimer's/Parkinson's disease management. CAs from pathogenic bacteria, fungi, protozoans and nematodes started to be considered as drug targets in recent years, with notable advances registered ultimately. CAIs have a complex multipharmacology probably unique to this enzyme, which has been exploited intensely but may lead to other relevant applications in the future, due to the emergence of drug design approaches which afforded highly isoform-selective compounds for most α-CAs known to date. They belong to a multitude of chemical classes (sulfonamides and isosteres, (iso)coumarins and related compounds, mono- and dithiocarbamates, selenols, ninhydrines, boronic acids, benzoxaboroles, etc). The polypharmacology of CAIs will also be discussed since drugs originally discovered for the treatment of non-CA related conditions (topiramate, zonisamide, celecoxib, pazopanib, thiazide and high-ceiling diuretics) show efective inhibition against many CAs, which led to their repurposing for diverse pharmacological applications. Significance Statement Carbonic anhydrase inhibitors have multiple pharmacologic applications as diuretics, antiglaucoma, antiepileptic, antiobesity, anti-acute mountain sickness, anti-idiopathic intracranial hypertension and as antitumor drugs. Their use in inflammatory conditions, cerebral ischemia, neuropathic pain, or neurodegenerations started to be investigated recently. Parasite carbonic anhydrases are also drug targets for antiinfectives with novel mechanisms of action which can by pass drug resistance to commonly used such agents. Drugs discovered for the management of other conditions that effectively inhibit these enzymes exert interesting polypharmacologic effects.

Discovery of Arylpiperazines with Broad-Spectrum Antimicrobial Activity and Favorable Pharmacokinetic Profiles.

Microorganisms can induce diseases with significant clinical implications for human health. Multidrug-resistant microorganisms have been on the rise worldwide over the past few decades, and no new antibiotics have been introduced to the market in a considerable amount of time. Such situation highlights the urgency of discovering new antimicrobial drugs to address this pressing issue. Therefore, the objective of this study was to identify bioactive compounds against 15 species of bacteria and 5 species of fungi of clinical relevance through in vitro screening of 58 synthetic compounds from four chemical classes of our internal library of synthetic compounds. Our findings highlight arylpiperazines 18, 20, 26, 27, and 29, and the aminothiazole 50, as potent broad-spectrum antimicrobials (MICs = 12.5 - 15.6 mg.mL-1) against clinically relevant bacteria and fungi. Additionally, these compounds displayed low cytotoxicity against various host cells and a favorable in vitro pharmacokinetic profile for oral administration. Indeed, all six showed adequate lipophilicity, high gastrointestinal permeability, metabolic stability in human and mouse liver microsomes, and satisfactory aqueous solubility. Thus, they emerge as promising starting points for hit-to-lead studies towards new antibacterial and antifungal agents, especially against Staphylococcus epidermidis, Staphylococcus aureus, Lactobacillus paracasei and Candida orthopsilosis.

Bimetallic nanocolloidal plasmonic array for polyphenol characterization and calibration-free antioxidant capacity evaluation.

Abimetallic plasmonic nanoparticles-based approach for the untargeted evaluation of phenolic compounds (PC)-pattern and antioxidant capacity (AoC) is proposed. The rationale relies on the PC's ability to drive the formation of bimetallic silver/gold nanocolloidal 'probes' with different conformations. Ag/Au bimetallic nanostructures, according to the PCs' amount and class, return characteristic plasmonic and colorimetric tags. Plasmonic indexes are proposed to assess the dominant PC classes, while the colorimetric response, analyzed simply by a smartphone, is employed to obtain an AoC score, withoutcalibration. The methods were tested with PCs belonging to different chemical classes, and challenged to classify different food samples.The proposed approach allows PC-dominant class identification and AoC-evaluation consistent with HPLC-MS/MS and conventional photometric assays.

Comparative Investigation of Punica granatum L. Phytochemical Analysis and In-vitro Antimicrobial Activity Screening Using Roots Samples from Urban and Rural Areas Uses Five Different Solvent Extracts .

Antimicrobial, fungal, and bacterial infections in the human body are the causes of foodborne, waterborne, and airborne illnesses as well as those that arise naturally. Because nosocomial usage increases the presence of both complex and non-complicated microorganisms, urinary tract infections (UTIs) are most common, especially in women. Antibiotics are an amazing tool in the fight against infections; the WHO survey 2022(1) noted that microbial and fungal infections account for 1.5 billion deaths worldwide. The production of natural remedies is becoming a serious concern and is progressing quickly as well. Many phytochemical compounds from flora could be used to treat these infections based on the effect of the respective integrated organism’s host defense efficacy. The therapeutic or pathogen-resistant capacity of the phytochemicals under different chemical classes may reverse and control the antibiotic resistance of resistant pathogens. The aim of the study is to find the roots of Punica granatum L from the urban and rural regions to find the phytochemical efficacy from extracts like petroleum ether, chloroform, ethanol, carbinol and aqueous. It revealed that a high yield of pharmacological compounds is from a rural sample’s carbinol extract. Quantitative analysis showed the presence of high amounts of majorly anti-cancerous agents in high peaks from rural samples. Using the well diffusion method, in-vitro antimicrobial activity was determined. Against their negative controls, the inhibition activity of Escherichia coli showed a 22 mm inhibition zone from the ethanol extract, Staphylococcus aureus showed a 21 mm inhibition zone, and fungal pathogens such as Candida albicans and Candida krusei showed a 21 mm maximum inhibition zone from the carbinol extracts.

Outstanding Scientist I. Ya. Horbachevsky (dedicated to the 170th birth anniversary)

Ivan Yakovych Horbachevsky is one of the outstanding scientists of world science, whose activities span the middle of the 20th century. He, our compatriot, comes from the village Zarubyntsi, Ternopil region. The numerous scientific and governmental titles, ranks and awards that he was awarded confirm Ivan Horbachevsky’s global authority and popularity. He was elected honorary president of international scientific forums and congresses. He was also entrusted with the most difficult tasks in medicine and education. The scientist brought recognition to University of Vienna. He was elected a member (and later chairman) of the Royal Sanitary Council, given several high titles and appointed the first minister of health in Austria-Hungary. Ivan Horbachevsky’s scientific heritage includes more than 50 works published in German, Czech and Ukrainian languages (only 6 of them were in Ukrainian). He proposed the nomenclature of organic (1924–1926) and inorganic compounds (1939–1941), which formed the basis of the chemical substance classification and nomenclature. His nomenclature was implemented in Ukraine before World War II. Ivan Yakovych Horbachevsky was a candidate for the Nobel Prize in Physiology and Medicine in 1911. He lived for 67 years outside of his motherland, but he was closely connected with Ukraine, and did a lot for our state independence.

Beyond Artists' Colors: A Spectral Reference Database for the Identification of β-Naphthol and Triarylcarbonium Colorants by MeVSIMS.

β-Naphthol and triarylcarbonium colorants were often used by modern and contemporary artists in materials such as inks and paints. Their poor stability and ability to fade upon exposure to light make their identification in artworks crucial for planning exhibitions and preventive conservation. Secondary ion mass spectrometry with MeV primary ions (MeV SIMS) is necessary when analyzing synthetic organic colorants (SOCs) with similar molecular structures due to its advantages in high sensitivity and soft ionization, which causes a low fragmentation of organic molecules. In this work, we applied MeV SIMS with 5 MeV Si4+ to identify selected β-naphthol and triarylcarbonium colorants from the 19th/20th century Materials Collection kept at the Academy of Fine Arts Vienna. The collection contains SOCs from renowned companies, such as I.G. Farben and I.C.I., and serves as a unique source of reference materials in the analysis of artworks. Previous research on these colorants with X-ray fluorescence analysis (XRF), micro-Raman, and Fourier transform infrared (FTIR) spectroscopies failed in the case of colorant mixtures. Similar spectral features of the SOCs within one chemical class and their low concentrations in mixtures did not lead to their identification using these techniques. MeV SIMS detected molecular ions or protonated molecules in the positive-ion mode. In the negative-ion mode, the functional groups (NO2 - and SO3 -) of β-naphthol lakes/pigments and heteropolyacid species (WO3 - and MoO3 -) characteristic of triarylcarbonium toners were determined. The results demonstrate that MeV SIMS is highly effective for identifying β-naphthol and triarylcarbonium colorants in mixtures and distinguishing between pigments, toners, lakes, and dyes.

Impact of Biotransformation on Internal Concentrations and Specificity Classification of Organic Chemicals in the Zebrafish Embryo (Danio rerio).

Internal concentrations (ICs) are crucial for linking exposure to effects in the development of New Approach Methodologies. ICs of chemicals in aquatic organisms are primarily driven by hydrophobicity and modulated by biotransformation and efflux. Comparing the predicted baseline to observed toxicity enables the estimation of effect specificity, but biological processes can lead to overestimating ICs and bias the specificity assessment. To evaluate the prediction of a mass balance model (MBM) and the impact of biotransformation on ICs, experimental ICs of 63 chemicals in zebrafish embryos were compared to predictions with physicochemical properties as input parameters. Experimental ICs of 79% (50 of 63) of the chemicals deviated less than 10-fold from predictions, and the remaining 13 deviated up to a factor of 90. Using experimental ICs changed the classification for 19 chemicals, with ICs 5 to 90 times lower than predicted, showing the bias of specificity classification. Uptake kinetics of pirinixic acid, genistein, dexamethasone, ethoprophos, atorvastatin, and niflumic acid were studied over a 96 h exposure period, and transformation products (TPs) were elucidated using suspect- and nontarget screening with UPLC-HRMS. 35 TPs (5 to 8 TPs per compound) were tentatively identified and semiquantified based on peak areas, suggesting that biotransformation may partly account for the overpredictions of ICs.

Development of amphiphilic hypercrosslinked porous polymers for magnetic extraction of multiple environmental pollutants in water

Under the principle of similar compatibility, researchers have developed various polarity extractants corresponding to a class of chemicals. Separating different polarities chemicals with one extractant effectively has become a novel research trend in separation science. Given the complexity of environmental sample matrices and the significant differences in polarity and solubility of various compounds, the introduction of hydrophilic groups to hydrophobic material skeletons can lead to sorbents with hydrophilic-lipophilic balance (HLB) property and thus improve their extraction performance for substances with different polarities. In this work, a hypercrosslinked polymer (HCPPz-TPB), designated as HLB, was synthesized by incorporating polar pyrazine and nonpolar triphenylbenzene molecules within each other. Subsequently, a core-shell magnetic composite material was obtained by encapsulating magnetic Fe3O4 nanoparticles in HCPPz-TPB. The material was applied as an adsorbent for magnetic solid phase extraction (MSPE) and combined with a high-performance liquid chromatography-photodiode array detector (HPLC-PDA) to enrich, separate, and detect seven polar contaminants in environmental water samples. The proposed approach, Fe3O4@SiO2@HCPPz-TPB−MSPE-HPLC-PDA, is characterized by its outstanding high sensitivity, low detection limits, wide linear range, and good reproducibility. The method demonstrated satisfactory linearity in the range of 0.05–2 μg mL-1 with R2 values between 0.9969 and 0.9997; the limits of detection (LOD) were observed to be within the range of 0.0019–0.016 μg L-1, and limits of quantification (LOQ) was observed to be within the range of 0.0064–0.054 μg L-1 range with good precision. The recoveries of the different contaminants in the environmental samples ranged from 83.61 to 116.46% (RSD≤10.56, n = 5). The new hydrophilic-lipophilic balance extractant is highly efficient, sensitive, and precise for extracting different polar pollutants. The findings demonstrate that the Fe3O4@SiO2@HCPPz-TPB display a remarkable affinity for multiple targets, driven by complex interactions including multi-stackings and hydrogen bonding as a sorbent. The synthesized Fe3O4@SiO2@HCPPz-TPB may be employed in diverse applications, including extraction, removal, and determination of diverse trace multi-target analytes in complex media.

Pyroptosis and chemical classification of pyroptotic agents.

Pyroptosis, as a lytic-inflammatory type of programmed cell death, has garnered considerable attention due to its role in cancer chemotherapy and many inflammatory diseases. This review will discuss the biochemical classification of pyroptotic inducers according to their chemical structure, pyroptotic mechanism, and cancer type of these targets. A structure-activity relationship study on pyroptotic inducers is revealed based on the surveyed pyroptotic inducer chemotherapeutics. The shared features in the chemical structures of current pyroptotic inducer agents were displayed, including an essential cyclic head, a vital linker, and a hydrophilic tail that is significant for π-π interactions and hydrogen bonding. The presented structural features will open the way to design new hybridized classes or scaffolds as potent pyroptotic inducers in the future, which may represent a solution to the apoptotic-resistance dilemma along with synergistic chemotherapeutic advantage.

UPLC‐MS/MS and chemometrics analyses reveal chemical profile and anti‐inflammatory activity of Bienertia cycloptera Bunge fractions

AbstractIntroductionBienertia cycloptera is a species belonging to the Chenopodiaceae family. According to earlier reports, a unique research study on the phytochemistry and biological analysis of that species was conducted.ObjectiveThis study presents an integrated metabolomics investigation combined with multivariate analysis of various extractive fractions of B. cycloptera aerial parts. This study is the first attempt to explore the anti‐inflammatory metabolites from B. cycloptera, showing its significance as a valuable traditional medicine.MethodologyBy comparing retention times, quasi‐molecular ions, and MS/MS fragment ions with databases and literature references, metabolite annotation was accomplished using ultra performance liquid chromatography (UPLC)/triple quadrupole mass spectrometry (MS). Moreover, the effects of the studied samples on the gene expression of the four pro‐inflammatory cytokines (IL‐1β, IL‐6, TNF‐α, and INF‐γ) using polymerase chain reaction (PCR) and comparing their results by those caused by piroxicam were tested to determine their anti‐inflammatory efficacy.ResultsChemical profiling revealed diverse metabolites, with 62 chromatographic peaks identified across various chemical classes. UPLC‐MS/MS of different B. cycloptera fractions unveiled distinct chemical profiles. Results showed distinct chemical compositions in each fraction, with petroleum ether fraction enriched in sterols and fatty acids; methylene chloride fraction in alkaloids, sterols, and cardenolides; ethyl acetate fraction in alkaloids, flavonoids, cardenolides, and phenolic acids; and n‐butanol fraction in flavonoids, alkaloids, and phenolic acids. Multivariate data analysis illustrated clustering patterns among petroleum ether, methylene chloride, ethyl acetate, and n‐butanol fractions. OPLS‐DA models were constructed to discern inter‐class differences, identifying discriminatory metabolites. In vitro cytotoxicity and anti‐inflammatory assays demonstrated the safety and efficacy of B. cycloptera fractions, with significant downregulation of pro‐inflammatory markers. Further analysis revealed specific metabolites associated with anti‐inflammatory effects, such as p‐hydroxybenzoic acid, vanillic acid, tachioside, ferulic acid, staphylionoside D, humilixanthin, bergaptol, vulgaxanthin I, and portulacaxanthin III.ConclusionThe findings of this study provide valuable insights into the chemical composition and bioactivity of B. cycloptera fractions, suggesting their potential as therapeutic agents and warranting further investigation.

Screening of DNMT3A inhibitors from phytochemicals using molecular docking and molecular dynamics simulation for their anti-cancer potential

ABSTRACT There is a consensus that epigenomic changes play a significant role in carcinogenesis. The effect of DNA methylation and its increased modulations on gene expression during carcinogenesis is significant for diagnostic and therapeutic purposes. Potential phytochemicals as anticancer approach modulators of epigenetic pathways are the focus of this investigation. Molecular docking studies were conducted to foretell how phytochemicals will interact with DNMT3A. As part of our effort to identify novel anti-cancer treatments, we examined a wide variety of phytochemicals from many chemical classes, including cannabinoids, carotenoids, chalcones, fatty acids, lignans, polysaccharides, saponins, steroids, and tannins. The docking scores for Dihydromyricetin are -10.207 kcal/mol, -9.313 kcal/mol for S-Adenosyl-L-methionine (SAM), and -8.757 kcal/mol for Zeylenol were determined to be superior than to phytochemical inhibitors against DNMT3A in the virtual screening method. Docking scores, hydrogen bond interactions, ADME characteristics, and DFT. Molecular Dynamics Simulation and free energy calculations demonstrated that these compounds bind stably to DNMT3A, potentially inhibiting its activity. Network Pharmacology suggested Dihydromyricetin's specific anticancer potential against cervical cancer. These findings provide insights into protein-Ligand interactions with Dnmt3A and highlights the need for In-vitro validation.

Targeting Plasmodium falciparum IspD in the Methyl-d-erythritol Phosphate Pathway: Urea-Based Compounds with Nanomolar Potency on Target and Low-Micromolar Whole-Cell Activity.

The methyl-d-erythritol phosphate (MEP) pathway has emerged as an interesting target in the fight against antimicrobial resistance. The pathway is essential in many human pathogens, including Plasmodium falciparum (Pf), but is absent in human cells. In the present study, we report on the discovery of a new chemical class targeting IspD, the third enzyme in the pathway. Exploration of the structure-activity relationship yielded inhibitors with potency in the low-nanomolar range. Moreover, we investigated the whole-cell activity, mode of inhibition, metabolic, and plasma stability of this compound class, and conducted in vivo pharmacokinetic profiling on selected compounds. Lastly, we disclosed a new mass spectrometry (MS)-based enzymatic assay for direct IspD activity determination, circumventing the need for auxiliary enzymes. In summary, we have identified a readily synthesizable compound class, demonstrating excellent activity and a promising profile, positioning it as a valuable tool compound for advancing research on IspD.

An in vitro and machine learning framework for quantifying serum albumin binding of per- and polyfluoroalkyl substances

Abstract Per- and polyfluoroalkyl substances (PFAS) are a diverse class of anthropogenic chemicals; many are persistent, bioaccumulative, and mobile in the environment. Worldwide, PFAS bioaccumulation causes serious adverse health impacts, yet the physiochemical determinants of bioaccumulation and toxicity for most PFAS are not well understood, largely due to experimental data deficiencies. As most PFAS are proteinophilic, protein binding is a critical parameter for predicting PFAS bioaccumulation and toxicity. Among these proteins, human serum albumin (HSA) is the predominant blood transport protein for many PFAS. We previously demonstrated the utility of an in vitro differential scanning fluorimetry assay for determining relative HSA binding affinities for 24 PFAS. Here, we report HSA affinities for 65 structurally diverse PFAS from 20 chemical classes. We leverage these experimental data, and chemical/molecular descriptors of PFAS, to build 7 machine learning classifier algorithms and 9 regression algorithms, and evaluate their performance to identify the best predictive binding models. Evaluation of model accuracy revealed that the top performing classifier model, logistic regression, had an AUROC statistic of 0.936. The top performing regression model, support vector regression, had an R2 of 0.854. These top performing models were then used to predict HSA-PFAS binding for chemicals in the EPAPFASINV list of 430 PFAS. These developed in vitro and in silico methodologies represent a high-throughput framework for predicting protein-PFAS binding based on empirical data, and generate directly comparable binding data of potential use in predictive modeling of PFAS bioaccumulation and other toxicokinetic endpoints.

Antimicrobial Activity of Arthrospira platensis-Mediated Gold Nanoparticles against Streptococcus pneumoniae: A Metabolomic and Docking Study.

The emergence of antibiotic-resistant Streptococcus pneumoniae necessitates the discovery of novel therapeutic agents. This study investigated the antimicrobial potential of green-synthesized gold nanoparticles (AuNPs) fabricated using Arthrospira platensis extract. Characterization using Fourier transform infrared spectroscopy revealed the presence of functional groups such as ketones, aldehydes, and carboxylic acids in the capping agents, suggesting their role in AuNP stabilization. Transmission electron microscopy demonstrated the formation of rod-shaped AuNPs with a mean diameter of 134.8 nm, as determined by dynamic light scattering, and a zeta potential of -27.2 mV, indicating good colloidal stability. The synthesized AuNPs exhibited potent antibacterial activity against S. pneumoniae, with a minimum inhibitory concentration (MIC) of 12 μg/mL, surpassing the efficacy of the control antibiotic, tigecycline. To elucidate the underlying mechanisms of action, an untargeted metabolomic analysis of the A. platensis extract was performed, identifying 26 potential bioactive compounds belonging to diverse chemical classes. In silico studies focused on molecular docking simulations revealed that compound 22 exhibited a strong binding affinity to S. pneumoniae topoisomerase IV, a critical enzyme for bacterial DNA replication. Molecular dynamics simulations further validated the stability of this protein-ligand complex. These findings collectively highlight the promising antimicrobial potential of A. platensis-derived AuNPs and their constituent compounds, warranting further investigation for the development of novel anti-pneumococcal therapeutics.