Identification Of Compounds Research Articles

Drosophila melanogaster as a model organism for screening acetylcholinesterase reactivators

ABSTRACT The widely used insecticide chlorpyrifos (CP) is known to inhibit acetylcholinesterase (AChE) activity attributed to result in various neurological disorders and acetylcholine-dependent organ functions including heart, skeletal muscle, lung, gastrointestinal tract, and central nervous systems. Enzyme reactivators, such as oximes, are known to restore AChE activity and mitigate adverse effects. The identification of compounds that reactivate AChE constitute agents with important therapeutic beneficial effects in cases of pesticide poisoning. However, the screening of novel drugs using traditional models may raise ethical concerns. This study aimed to investigate the potential of Drosophila melanogaster as a model organism for screening AChE reactivators, with a focus on organophosphate poisoning. The efficacy of several oximes, including pralidoxime, trimedoxime, obidoxime, methoxime, HI-6, K027, and K048, against CP-induced AChE activity inhibition in D. melanogaster was determined in silico, in vitro, and in vivo experiments. Molecular docking studies indicated a strong interaction between studied oximes and the active-site gorge of AChE. Data showed that selected oximes (100 μM) are effective in the reactivation of AChE inhibited by CP (10 μM) in vitro. Finally, in vivo investigations demonstrated that selected oximes, pralidoxime and K048 (1.5 ppm), reversed the locomotor deficits, inhibition of AChE activity as well as lowered the mortality rates induced by CP (0.75 ppm). Our findings contribute to utilization of D. melanogaster as a robust model for determination of actions of identified new AChE inhibitory agents with more effective therapeutic properties that those currently in use in the clinical practice in treatment of AChE associated disorders.

Recent Advances in Discovery, Structure, Bioactivity, and Biosynthesis of trans-AT Polyketides.

Bacterial trans-acyltransferase polyketide synthases (trans-AT PKSs) are among the most complex enzymes, which are responsible for generating a wide range of natural products, identified as trans-AT polyketides. These polyketides have received significant attention in drug development due to their structural diversity and potent bioactivities. With approximately 300 synthesized molecules discovered so far, trans-AT PKSs are found widespread in bacteria. Their biosynthesis pathways exhibit considerable genetic diversity, leading to the emergence of numerous enzymes with novel mechanisms, serving as a valuable resource for genetic engineering aimed at modifying small molecules' structures and creating new engineered enzymes. Despite the systematic discussions on trans-AT polyketides and their biosynthesis in earlier studies, the continuous advancements in tools, methods, compound identification, and biosynthetic pathways require a fresh update on accumulated knowledge. This review seeks to provide a comprehensive discussion for the 27 types of trans-AT polyketides discovered within the last seven years, detailing their sources, structures, biological activities, and biosynthetic pathways. By reviewing this new knowledge, a more profound understanding of the trans-AT polyketide family can be achieved.

Integrative analysis of the efficacy and pharmacological mechanism of Xuefu Zhuyu decoction in idiopathic pulmonary fibrosis via evidence-based medicine, bioinformatics, and experimental verification

ObjectiveWe used evidence-based medicine, bioinformatics and experimental verification to comprehensively analyze the efficacy and pharmacological mechanism of Xuefu Zhuyu decoction (XFZYD) in the treatment of idiopathic pulmonary fibrosis (IPF). MethodsMajor databases were retrieved for randomized controlled trials (RCTs) of XFZYD treating IPF to perform meta-analysis. Active ingredients and target genes of XFZYD were identified from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). IPF-related differentially expressed genes (DEGs) were identified from the Gene Expression Omnibus (GEO) database. The RGUI software was utilized for Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The ingredient-target and protein-protein interaction (PPI) networks were achieved through Cytoscape software and the STRING database to identify the key compounds and target proteins. Molecular docking was performed using AutoDockTool and AutoDock Vina software. The effect between key compounds and target proteins was verified in animal experiments. ResultsSix RCTs were included for meta-analysis, which uncovered that the total effective rate of clinical efficacy was higher in the experimental group than control group. Then, 156 active ingredients and 254 target genes of XFZYD, and 1,566 IPF-related DEGs were identified. The intersection analysis identified 48 target genes correlating with 130 active ingredients of XFZYD treating IPF. GO functional enrichment, KEGG pathway enrichment, ingredient-target network and PPI network were achieved. Following the identification of key compounds and target proteins, we performed molecular docking. Ultimately, our research focused on the key compound quercetin for experimental validation to assess its interactions with two key target proteins, JUN and PTGS2. ConclusionThe effectiveness of XFZYD on IPF has been substantiated through evidence-based medicine. The pharmacological mechanism of XFZYD for IPF treatment involves a complex interplay of various compounds and targets, with quercetin exerting pronounced impacts on JUN and PTGS2 proteins.

SPME arrow-based extraction for enhanced targeted and untargeted urinary volatilomics

BackgroundVolatile organic compounds (VOCs) present in human urine are promising biomarkers for various health conditions and environmental exposures. However, their reliable detection is challenging due to the complexity of urinary matrices and the low concentrations of VOCs. Moreover, untargeted approaches present considerable challenges in terms of data interpretation, increasing the complexity of method development. Here we address these challenges by developing a new method that combines solid-phase microextraction (SPME) Arrow with gas chromatography-high resolution mass spectrometry (GC-HRMS), using a design of experiments (DOE) approach for targeted and untargeted compounds. This methodology, specifically tailored for SPME Arrow, represents a significant advancement in untargeted urinary analysis. ResultsThe method was developed based on targeted and untargeted outcomes, were ranking results focus on the highest response area of 11 spiked target VOCs representative of urinary volatilomics, and on identifying the maximum untargeted number of VOCs. The method was developed focusing on the highest response area of 11 spiked target VOCs representative of urinary volatilomics and identifying the maximum number of VOCs. A univariate method determined the optimal coating type, urine volume, and salt addition. Subsequently, a central composite design (CCD) DOE was used to determine ideal temperature, extraction, and incubation times. The best method obtained has an extraction time of 60 min at a temperature of 53 °C, with an SPME Arrow CAR/PDMS using 2 mL of urine, with 0.25 % w/v of NaCl and a pH of 2. Compared to conventional SPME fibers, the SPME Arrow showed improved extraction efficiency, detecting more VOCs. Finally, the enhanced method was successfully applied to urine samples from children exposed and non-exposed to tobacco smoke, identifying specific VOCs, like p-cymene and p-isopropenyl toluene related to tobacco exposure. SignificanceBy integrating both targeted and untargeted approaches, the developed method comprehensively captures the complexity of urinary metabolomics. This dual strategy ensures the precise identification of known compounds and the discovery of novel biomarkers, thereby providing a more complete metabolic profile. Such an approach is crucial for advancing in non-invasive diagnostics and environmental health studies, as it offers deeper insights into the intricate relationships between metabolic processes and various health conditions.

Differential cytotoxic effects of Garcinia mangostana pericarp extract on leukaemic versus normal human cell lines: insights into selective anticancer activity

IntroductionGarcinia mangostana L. is widely recognised for its traditional medicinal uses and growing relevance in the nutraceutical sector. This research endeavour is designed to scrutinise the phytochemical composition and cytotoxic effects of an alcoholic extract derived from the pericarps of G. mangostana (ME) on leukaemic cell lines. MethodsG. mangostana L. pericarps were subjected to ethanol extraction, and subsequent compound identification was conducted via Capillary Liquid Chromatography-Electrospray Ionisation-Quadrupole Time-of-Flight Tandem Mass Spectrometry (CapLC-ESI-QTOF-MS/MS). In parallel, the extract was fractionated through High-Performance Liquid Chromatography (HPLC). Furthermore, U937, Jurkat and normal human umbilical vein endothelial cell (HUVEC) lines were exposed to varying concentrations of the extract to assess cell proliferation, viability, cytotoxicity, and apoptotic DNA damage. ResultsInvestigations confirmed the presence of various xanthones, including β-mangostin, α-mangostin, and garcinone E. Significantly, ME displayed pronounced cytotoxic effects specifically on leukaemic cells, distinguishing its impact on malignant cells as opposed to non-malignant ones, and facilitated apoptotic DNA fragmentation. Moreover, the whole extract consistently displayed greater cytotoxicity compared to individual fractions. ConclusionAccording to the results obtained ME selective cytotoxicity against cancer cell lines and greater biological activity than the single compounds in the extract. These findings underscore ME's potential in cancer prevention, complementing dietary strategies ahead of pharmaceutical interventions.

RNA-Binding Small Molecules in Drug Discovery and Delivery: An Overview from Fundamentals.

RNA molecules, similar to proteins, fold into complex structures to confer diverse functions in cells. The intertwining of functions with RNA structures offers a new therapeutic opportunity for small molecules to bind and manipulate disease-relevant RNA pathways, thus creating a therapeutic realm of RNA-binding small molecules. The ongoing interest in RNA targeting and subsequent screening campaigns have led to the identification of numerous compounds that can regulate RNAs from splicing, degradation to malfunctions, with therapeutic benefits for a variety of diseases. Moreover, along with the rise of RNA-based therapeutics, RNA-binding small molecules have expanded their application to the modification, regulation, and delivery of RNA drugs, leading to the burgeoning interest in this field. This Perspective overviews the emerging roles of RNA-binding small molecules in drug discovery and delivery, covering aspects from their action fundamentals to therapeutic applications, which may inspire researchers to advance the field.

GPCRSPACE: A New GPCR Real Expanded Library Based on Large Language Models Architecture and Positive Sample Machine Learning Strategies.

The quest for novel therapeutics targeting G protein-coupled receptors (GPCRs), essential in numerous physiological processes, is crucial in drug discovery. Despite the abundance of GPCR-targeting drugs, many receptors lack selective modulators, indicating a significant untapped therapeutic potential. To bridge this gap, we introduce GPCRSPACE, a novel GPCR-focused purchasable real chemical library developed using the G protein-coupled receptors large language models (GPCR LLM) architecture. Different from traditional machine learning models, GPCR LLM uses a positive sample machine learning strategy for training and does not need to construct any negative samples. This not only reduces false negatives but also reduces the time to label negative samples. GPCR LLM accelerates the identification and screening of potential GPCR-interactive compounds by learning the chemical space of GPCR-targeting molecules. GPCRSPACE, built on GPCR LLM, outperforms existing chemical data sets in synthesizability, structural diversity, and GPCR-likeness, making it a valuable tool for GPCR drug discovery.

Bioactive Insecticides from Chemometric Diverse Ant-Associated Symbionts Streptomyces novaecaesareae and Streptomyces nojiriensis against the Fall Armyworm Larvae.

The Streptomyces genus has long been recognized as a prolific and valuable source of diverse secondary metabolites. These metabolites contribute significantly to the intricate chemical diversity exhibited by Streptomyces, making them an indispensable reservoir for drug discovery, agricultural applications, and industrial processes. Exploiting the potential of these natural compounds holds the promise of ushering in a new era in insect pest management, reducing reliance on synthetic chemicals and fostering ecologically sustainable solutions. This study dives into the realm of chemo diversity within isolates of Streptomyces nojiriensis and Streptomyces novaecaesareae, with a specific focus on the production of insecticidal compounds. We explored chromatographic techniques for the identification and isolation of insecticidal compounds, and two bioactive compounds were identified in extracts of S. novaecaesareae. Valinomycin was identified from hexanic extracts of strain Asp59, while naphthomycin from ethyl acetate extracts of strain Asp58. These compounds showed insecticidal activity against first instars of Spodoptera frugiperda (Asp59: LC50 = 10.82 µg/µL, LC90 = 26.25 µg/µL; Asp58: LC50 = 15.05 µg/µL, LC90 = 38.84 µg/µL). Notably, this is the first report of naphthomycin as an insecticidal compound. The present study suggests that valinomycin and naphthomycin may be a novel biological source for the control of Spodoptera frugiperda in early stages.

Rapid discovery of natural antioxidants in Hypericum japonicum: Dual roles of the liquid phase mobile phase as extraction and separation solvent

Hypericum japonicum is a traditional folk medicine with various bioactivities such as hepatoprotective, antioxidant, and anti-tumorous. The antioxidant effect of H. japonicum is one of the most prominent effects due to its responsibility for many of its activities. To clarify active natural substance, the antioxidant properties of H. japonicum were preliminarily assessed by ferric reducing–antioxidant power (FRAP), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) and Oxygen radical absorbance capacity (ORAC), as well as superoxide dismutase (SOD). Then, a straightforward and effective method named online liquid extraction-high performance liquid chromatography combined with ABTS antioxidant assay and mass spectrometry (OLE-HPLC-ABTS/Q-TOF-MS) was developed to swiftly and directly discover the antioxidants in H. japonicum. Using mobile phase as extraction and separation reagent, coupled with online activity analysis and compounds identification by high-resolution MS, the online system enables rapid screening of natural antioxidant bioactives from complex mixture. By using it, a total of 9 compounds including flavonoids and phenolic acids characterized by retention time, precise mass, and fragmentation ions in MS/MS spectra showed antioxidant action. Finally, the antioxidant and SOD activity of main found active compounds were validated by in vitro experiment assay and molecular docking. In summary, these results suggested that H. japonicum could be considered as a potential source of natural antioxidants, and the online integrated system might become a promising candidate for the natural antioxidants discovery in the future.

Identification of pyrimidine structure-based compounds as allosteric ligands of the dopamine transporter as therapeutic agents for NeuroHIV.

The disruption of dopamine neurotransmission by the HIV-1 Transactivator of transcription (Tat) during HIV-1 infection has been linked to the development of neurocognitive disorders, even under combined antiretroviral therapy (cART) treatment. We have demonstrated that SRI-32742, a novel allosteric modulator of dopamine (DA) transporter (DAT), attenuates cocaine- and Tat-binding to DAT, alleviates Tat-induced cognitive deficits and potentiation of cocaine reward in inducible Tat transgenic mice. The current study determined the in vitro pharmacological profile of SRI-32743 and its optimized second-generation analogs and their effects as allosteric modulators. Through structure-activity relationship studies of SRI-32743, 170 compounds were synthesized and evaluated for their ability to modulate DAT function. We identified 21 analogs as atypical competitors of DAT (Emax {less than or equal to}60%). Four compounds, SRI-46564, SRI-47056, SRI-46286 and SRI-47867, displayed IC50 values for [3H]DA uptake inhibition from 9.33 {plus minus} 0.50 to 0.96 {plus minus} 0.05 µM and from 3.96 {plus minus} 1.36 to 1.29 {plus minus} 0.19 for DAT binding, respectively. The four analogs also displayed high potency at two different concentrations (0.5 nM and 0.05 nM) to attenuate Tat-induced inhibition of [3H]DA uptake and cocaine-mediated dissociation of [3H]WIN35,428 binding in CHO cells expressing hDAT, suggesting that the effects occur through an allosteric mechanism. In further ex vivo studies using Fast-Scan Cyclic Voltammetry, we demonstrated that the analogs do not disrupt the baseline phasic-like DA release. These findings provide a new insight into the potential for development of novel therapeutic agents to attenuate DAT-Tat interactions to normalize DA neurotransmission in NeuroHIV. Significance Statement The allosteric inhibition of the dopamine (DA) transporter by the HIV-1 Transactivator of transcription (Tat) disrupts dopamine homeostasis, leading to HIV-associated neurocognitive disorders (HANDs). Analogs of SRI-32743, a novel allosteric modulator of the Tat-DAT interaction, were evaluated in the current study and characterized as atypical ligands of DA uptake. Four novel lead compounds demonstrated high potency to attenuate Tat-induced inhibition of hDAT-mediated DA uptake in an allosteric modulatory manner with no effects on the dynamics of DA uptake-release in DAT.

Identification of Pops Organic Compounds in Sediment in the Cisangkuy Watershed Using GC-MS Analysis Method

The Cisangkuy Watershed is a tributary of the Upper Citarum River located in the Bandung Basin, West Java. Based one previous research, one organic pollution in the Cisangkuy Watershed is the presence of POPs (Persistent Organic Pollutants) compounds. POPs are organic compounds that can last a very long time in the environment (persistent) and have toxic properties for organisms. This study aims to identify and analyse the organic content of POPs and sediments in the Cisangkuy Watershed, as well as to analyse the source of pollutants and categorise them based on the Stockholm Convention on Persistent Organic Pollutants. Identification of POPs compounds using gas chromatography-mass spectrometry (GC-MS) technique. Sediment sampling was conducted by grab sampling that involved 20 sampling points from upstream to downstream of the Cisangkuy Watershed (CS-1 to CS-20). Samples were collected from 9 sub-districts. The research location shows that the land activities at the sampling point include asphalt hot mix, pharmaceutical, textile, and manufacturing industries. The results showed the presence of 1,2-Benzenedicarboxylic acid, mono (2-ethylhexyl) ester, 4,8,12-Tetradecatrienenitrile, 5,9,13-trimethyl-, and 2-Hexyl-1-octanol compounds at sampling points from upstream to downstream. These compounds were derived from chemical industry effluents, fossil fuel combustion, and agricultural activities. The compounds are classified as ‘industrial waste’ and ‘industrial waste with antibiotic properties’ by the Stockholm Convention on Organic Waste Management.

Virtual design and screening of new (+)-catechin derivates N- and/or S-heterocyclic fragment for anti-malarial and anti-SARS-CoV-2 activities by In silico simulation

Hemisynthesis makes it possible to improve the activity or reduce the toxicity of a biocompound by modifying or adding peripheral groups. Catechin present in different plant species was known for its moderate anti-malarial and anti-SARS-CoV-2 activities. The aim of this work was focused on the identification of new compounds with potential anti-SARS-CoV-2 and/or anti-malarial activities, evaluated through In silico simulation. A polyphenol pharmacophore model, based on (+)-catechin (1) was virtually constructed using previously reported inhibitors. N- and/or S-heterocyclic fragments were inserted on the backbone of (+)-catechin and 12 pharmacophore hypotheses were studied. This study targeted 3 proteins biologically responsible for SARS-CoV-2 (PDB ID: 7JYC, 6M0J, and 6HZD) and one protein responsible for malaria (PDB ID: 3SRJ). Molecular docking had shown that the new catechin-aldehyde candidates have good Ligand-Protein affinity in terms of free energy compared to the study reference Narlaprevir and Artesunate for SARS-CoV-2 and malaria respectively. Theoretically, most compounds didn’t show toxicity except compounds 2a, 2i, and 2k, exhibiting hepatotoxic activity. Molecular dynamics was used to prove and assess their binding stability to the target protein for each activity. The 3SRJ-2f and 6HZD-2l structures were selected for anti-malarial and anti-SARS-CoV-2 activity respectively. The 3SRJ-2f and 6HZD-2l complexes showed stable interactions to 100 ns between the inhibitor fragments and the residual amino acids of the protein. To conclude, these novel compounds are probably to become promising lead molecules for the development of effective anti-SARS-CoV-2 and/or anti-malarial of all drugs. Keywords: Catechin, Anti-malarial, Anti-SARS-CoV-2, Docking and Dynamic Molecular, ADMET Analysis.

Bioassay guided isolation and compounds identification of the anti-diabetic fractions of (rosemary) Rosmarinus officinalis leaves extract

BackgroundDiabetes mellitus is a metabolic disease characterized by prolonged elevated blood glucose levels. It is a common health problem with a high mortality and morbidity to the human race. A number of medicinal plants such as rosemary (Rosmarinus officinalis) have been used for the treatment of diabetes. Most of the anti-diabetic conventional drugs have been found to have some side effects and there is therefore need to explore new sources of anti-diabetic drugs. The aim of the current study was to investigate the possibility of getting anti-diabetic compounds from R. officinalis that can be used as leads for drug discovery.MethodologyR. officinalis leaves were macerated in 50% methanol in dichloromethane and the crude extract fractionated by column chromatography. The obtained fractions were subjected to an in-vitro alpha-amylase inhibition assay. The anti-hyperglycemic potential of the fractions was evaluated in diabetic induced Wistar rats. The most potent fractions were analyzed by gas chromatography-mass spectrophotometry (GC-MS) for identification of the compounds.ResultsA total of 21 chromatographic fractions were assembled with different alpha- amylase inhibition activity. Eleven of the fractions had more than 30% alpha-amylase inhibition activity. The ethyl acetate fraction had the highest inhibition potential (LC50 of 2.8 μg/mL). The anti-diabetic assay in rats showed that fractions (F1) and (F4) had highest blood glucose reduction of 44.5 ± 0.4 and 52.8 ± 1.3%, respectively (p < 0.05). GC-MS analysis of fractions F1 and F4 showed the presence of 21 and 23 compounds in F1 and 23, respectively.ConclusionThis study has demonstrated that R. officinalis crude extract fractions obtained from 50% methanol in dichloromethane possesses alpha-amylase inhibitory and anti-hyperglycemic activities as well as secondary metabolites with varying chemical structures. The hexane and hexane/ethyl acetate (8/2) fractions showed most potent alpha-amylase inhibition with high anti-hyperglycemic activity giving hope of a possibility of obtaining lead compounds for new anti-diabetic drugs.

In vitro, bioassay guided identification of anticancer compounds from Vitex negundo Linn. Leaf using T98 glioma cells

Gliomas, the most devastating of brain tumours, pose immense therapeutic challenges due to the adverse effects of standard chemotherapeutic drugs. Seeking alternatives, natural products have emerged as promising sources for cancer treatment. Vitex negundo, a significant medicinal plant in traditional medicine, offers potential remedies for various ailments. In this study, fractionation via column chromatography we isolated fraction #25 from leaves of Vitex negundo. Employing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, wound healing assay, flow cytometry for cell cycle analysis, and HRLC-MS for compound identification, we investigated its effects on glioma cells. Results indicate that fraction #25 significantly reduces glioma cell viability and proliferation, inhibits cell migration in a dose-dependent manner, and arrests the cell cycle at G1 phase. Compound analysis reveals the presence of potent antiproliferative agents, including 7-hydroxy-3,4,5,6,8-pentamethoxyflavone, Virol-B, Momordin Ia, and Oryzalexin A. These findings underscore the potential of Vitex negundo as a source of anticancer compounds against glioma cells.

Rapid Targeted Screening and Identification of Active Ingredients in Herbal Extracts through Ligand-Detected NMR and Database Matching.

Herbal extracts are rich sources of active compounds that can be used for drug screening due to their diverse and unique chemical structures. However, traditional methods for screening these compounds are notably laborious and time-consuming. In this manuscript, we introduce a new high-throughput approach that combines nuclear magnetic resonance (NMR) spectroscopy with a tailored database and algorithm to rapidly identify bioactive components in herbal extracts. This method distinguishes characteristic signals and structural motifs of active constituents in the raw extracts through a relaxation-weighted technique, particularly utilizing the perfect echo Carr-Purcell-Meiboom-Gill (peCPMG) sequence, complemented by precise 2D spectroscopic strategies. The cornerstone of our approach is a customized database designed to filter potential compounds based on defined parameters, such as the presence of CHn segments and unique chemical shifts, thereby expediting the identification of promising compounds. This innovative technique was applied to identifying substances interacting with choline kinase α (ChoKα1), resulting in the discovery of four new inhibitors. Our findings demonstrate a powerful tool for unraveling the complex chemical landscape of herbal extracts, considerably facilitating the search for new pharmaceutical candidates. This approach offers an efficient alternative to traditional methods in the quest for drug discovery from natural sources.

Identification of novel antimicrobial compounds in colostrum-associated Lactiplantibacillus plantarum ZFS 1 and 2 by integrating in vitro, machine learning and bioinformatics approaches

Current study was designed to identify safe, novel antimicrobial compounds in the cell free supernatant of two colostrum-associated probiotic strains, “Lactiplantibacillus plantarum, ZFS-1 and ZFS-2” by using in vitro, advanced machine learning, and bioinformatics approaches. The cell free supernatant (CFS) and ethyl acetate fraction of CFS of both isolates, were evaluated for antagonistic properties against four pathogens. The antioxidant and anti-inflammatory properties of ethyl acetate fraction were also assessed in vitro. The secondary metabolites in the ethyl acetate fraction of CFS were identified by Gas chromatography-Mass spectrometry. Further, Machine learning techniques, including models such as Support Vector Machine, k-Nearest Neighbor, Naive Bayes, and Random Forest, were applied to analyze the data using Python. Molecular descriptors were calculated using the RDKit library and further analyzed through Principal Component Analysis. Among the models, the RF achieved 100% accuracy on the test set, with a 10-fold cross-validation accuracy of 93.84%. Additionally, docking analysis was conducted to evaluate the binding affinities between the identified metabolites and microbial proteins. The CFS of both isolates displayed inhibition zones of 12–18 mm, while ethyl acetate fraction exhibited ZI of 16–30 mm against four pathogens. Minimal Inhibitory and bactericidal concentrations ranged from 3.12 to 6.5 and 6.5–12.5 mg/mL, respectively. Significant differences (p < 0.05) were noted in their antimicrobial and antioxidant efficiencies. Acridine, 1H-Phenalen-1-one, and (NE)-N-[(4-amino-1,2,5-oxadiazol-3-yl)-(triazirin-1-yl)methylidene]hydroxylamine in CFS of Lactiplantibacillus plantarum strain ZFS-1 and 5,6,7,8-tetrahydro-2-methoxy-5,5-dimethyl-1,4-Anthracenedione in CFS of strain ZFS-2 were identified as novel antimicrobial compounds. The compounds are validated as potentially safe drug candidates employing comprehensive molecular docking analyses.

Comprehensive assessment of fragrance profiles in peony flowers through HS-GC-IMS and metabolic pathway analysis

This study addresses the identification and comparison of volatile organic compounds (VOCs) in different peony varieties to elucidate their distinct aroma profiles and the common VOCs that constitute the unique fragrance of peony flowers, laying a foundation for breeding high-quality peony varieties and developing related products. Headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS) combined with principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) was employed to analyze and differentiate the VOCs of eight peony varieties: TAOXI, ZIHELIAN, BAITIANE, YAOHUANG, DAFUGUI, DAOJIN, HONGXIUQIU, and MANAOPAN. The study identified 87 VOCs, revealing significant differences in VOC compositions among the samples. Notably, BAITIANE displayed distinct differences in both color and VOC composition compared to the other seven varieties. It exhibited uniquely high levels of butanoic acid-M, butanoic acid-D, hexanal-D, ethanol-D, and ethyl acetate. Twelve key differential VOCs were identified as having significant impacts: ethanol-D, hexanal-D, (e)-2-hexenal-D, (e)-2-hexenal-M, hexanal-M, butanoic acid-M, acetic acid-D, acetic acid-M, butanoic acid-D, ethyl acetate, thiophene, and dimethyl sulfide. KEGG pathway analysis highlighted the roles of xenobiotics biodegradation, terpenoid metabolism, and amino acid metabolism in VOC biosynthesis. The findings are significant for the breeding of fragrant peony varieties and the development of floral-based products. The findings provide theoretical support for breeding new horticultural flower varieties and developing commercial peony products, enhancing the understanding of floral scent chemistry, and offering valuable information for the perfumery, floral food processing, and related industries.

Influence of fractionation of polyphenols by membrane chromatography on antioxidant, antimicrobial and proliferation-inhibiting effects of red fruit juices

Interest in fruit juice extracts as nutraceuticals is constantly increasing due to their health-beneficial properties, mainly caused by polyphenols. However, the correlation between the various effects of fruit juice extracts and their individual composition, including anthocyanins and copigments, is unknown. Therefore, in the present study, eight red fruit juice extracts were prepared using XAD-7 column chromatography, followed by fractionation and identification of the different compounds as well as characterization of their health-promoting effects. The fruit juice extract of pomegranate, chokeberry, and cranberry showed the highest antimicrobial potential against food-borne pathogens. The highest antioxidant and cell proliferation-inhibiting potential was also found in the pomegranate extract. It can be assumed that pomegranate extracts, which are rich in copigments, especially hydrolyzable tannins, are suitable natural antioxidants and antimicrobial agents. Pomegranate extracts could be used as nutraceuticals or natural preservatives.

Identification of Compounds That Contribute to Consumer Aroma Liking of Roasted American-European Hybrid Hazelnuts.

New interspecific hybrid hazelnut crosses between American (Corylus americana) and European (Corylus avellana) hazelnuts are being developed to support a commercial industry in the Midwest region of the United States. In this study, volatile compounds that impact consumer aroma liking of roasted hybrid hazelnuts (C. americana × C. avellana) were investigated by targeted and nontargeted GC/MS flavoromics. Chemical profiles from 10 roasted hybrid hazelnut samples were modeled with consumer aroma liking scores by orthogonal partial least-squares with good fit and predictive performance (R2 ≥ 0.92, Q2 ≥ 0.82, RMSECV = 0.2). Top ranked predictors positively correlated with liking included 12 aroma compounds and 4 profiled volatiles for the targeted and nontargeted methods, respectively. Sensory recombination testing of hazelnut samples with addition of the 12 predictive odorants was preferred by consumers (p < 0.001, Δ aroma liking = 2.2 on 9-point scale) and perceived as more roasty, nutty, and sweet compared to the control (p < 0.05). Addition of the 4 predictive volatiles at subthreshold levels also was preferred (p = 0.02) and perceived as less earthy and mushroom like than the control (p < 0.05).

Electrochemical stability of biodegradable Zn-Cu alloys through machine-learning accelerated high-throughput discovery.

Zn-Cu alloys have attracted great attention as biodegradable alloys owing to their excellent mechanical properties and biocompatibility, with corrosion characteristics being crucial for their suitability for biomedical applications. However, the unresolved identification of intermetallic compounds in Zn-Cu alloys affecting corrosion and the complexity of the application environment hamper the understanding of their electrochemical behavior. Utilizing high-throughput first-principles calculations and machine-learning accelerated evolutionary algorithms for screening the most stable compounds in Zn-Cu systems, a dataset encompassing the formation energy of 2033 compounds is generated. It reveals that most of the experimentally reported Zn-Cu compounds can be replicated, especially the structure of R32 CuZn5 is first discovered which possesses the lowest formation energy of -0.050 eV per atom. Furthermore, the simulated X-ray diffraction pattern matches perfectly with the experimental ones. By formulating 342 potential electrochemical reactions based on the binary compounds, the Pourbaix diagrams for Zn-Cu alloys are constructed to clarify the fundamental competition between different phases and ions. The calculated equilibrium potential of CuZn5 is higher than that of Zn through the forward reaction Zn + CuZn5 ⇌ CuZn5 + Zn2+ + 2e-, resulting in microcell formation owing to the stronger charge density localization in Zn compared to CuZn5. The presence of chlorine accelerates the corrosion of Zn through the reaction Zn + CuZn5 + 6Cl- + 6H2O ⇌ Cu + 6ZnOHCl + 6H+ + 12e-, where the formation of ZnOHCl disrupts the ZnO passive film and expands the corrosion pH range from 9.2 to 8.8. Our findings reveal an accurate quantitative corrosion mechanism for Zn-Cu alloys, providing an effective pathway to investigate the corrosion resistance of biodegradable alloys.