Inhibition Capability Research Articles

Electrochemical behaviour of sputter-coated titanium films on AZ31 magnesium alloy

Lightweight magnesium-based structural alloy AZ31 is normally prone to high corrosion in an aqueous environment. A detailed study is reported in this work on AZ31 Mg alloy coated with Ti thin films of different thicknesses by DC sputtering to investigate the capability of Ti coating to prevent corrosion of AZ31 under an aqueous environment similar to seawater. Ti films have been fabricated to 50, 100 and 150 nm thicknesses. Utilising grazing incidence-XRD and SEM, the films’ structure and microstructure were studied. The films were amorphous. Due to corrosion, interesting micro-structures evolved. Corrosion inhibition characteristics of the Ti films were characterised by electrochemical techniques such as potentiodynamic polarisation and impedance spectroscopy. Ti films with 100 nm and 150 nm thickness show a good inhibition capability. The corrosion mechanism was investigated using XPS and X-ray energy dispersive spectra.

Primary Antioxidant Power and Mpro SARS-CoV-2 Non-Covalent Inhibition Capabilities of Miquelianin.

The antioxidant power of quercetin-3-O-glucuronide (miquelianin) has been studied, at the density functional level of theory, in both lipid-like and aqueous environments. In the aqueous phase, the computed pKa equilibria allowed the identification of the neutral and charged species present in solution that can react with the ⋅OOH radical. The Hydrogen Atom Transfer (HAT), Single Electron Transfer (SET) and Radical Adduct Formation (RAF) mechanisms were considered, and the individual, total and fraction corrected rate constants were obtained. Potential non-covalent inhibition of Mpro from SARS-CoV-2 by miquelianin has been also evaluated.

Exploring the anti-gout potential of sunflower receptacles alkaloids: A computational and pharmacological analysis

Gout, a painful condition marked by elevated uric acid levels often linked to the diet's high purine and alcohol content, finds a potential treatment target in xanthine oxidase (XO), a crucial enzyme for uric acid production. This study explores the therapeutic properties of alkaloids extracted from sunflower (Helianthus annuus L.) receptacles against gout. By leveraging computational chemistry and introducing a novel R-based clustering algorithm, “TriDimensional Hierarchical Fingerprint Clustering with Tanimoto Representative Selection (3DHFC-TRS)," we assessed 231 alkaloid molecules from sunflower receptacles. Our clustering analysis pinpointed six alkaloids with significant gout-targeting potential, particularly emphasizing the fifth cluster's XO inhibition capabilities. Through molecular docking and the BatchDTA prediction model, we identified three top compounds—2-naphthylalanine, medroxalol, and fenspiride—with the highest XO affinity. Further molecular dynamics simulations assessed their enzyme active site interactions and binding free energies, employing MM-PBSA calculations. This investigation not only highlights the discovery of promising compounds within sunflower receptacle alkaloids via LC-MS but also introduces medroxalol as a novel gout treatment candidate, showcasing the synergy of computational techniques and LC-MS in drug discovery.

Selective and Scalable CO2 Electrolysis Enabled by Conductive Zinc Ion-Implanted Zeolite-Supported Cadmium Oxide Nanoclusters.

Catalyst supports play an essential role in catalytic reactions, hinting at pronounced metal-support effects. Zeolites are a propitious support in heterogeneous catalysts, while their use in the electrocatalytic CO2 reduction reaction has been limited as yet because of their electrically insulating nature and serious competing hydrogen evolution reaction (HER). Enlightened by theoretical prediction, herein, we implant zinc ions into the structural skeleton of a zeolite Y to strategically tailor a favorable electrocatalytic platform with remarkably enhanced electronic conduction and strong HER inhibition capability, which incorporates ultrafine cadmium oxide nanoclusters as guest species into the supercages of the tailored 12-ring window framework. The metal d-bandwidth tuning of cadmium by skeletal zinc steers the extent of substrate-molecule orbital mixing, enhancing the stabilization of the key intermediate *COOH while weakening the CO poisoning effect. Furthermore, the strong cadmium-zinc interplay causes a considerable thermodynamic barrier for water dissociation in the conversion of H+ to *H, potently suppressing the competing HER. Therefore, we achieve an industrial-level partial current density of 335 mA cm-2 and remarkable Faradaic efficiency of 97.1% for CO production and stably maintain Faradaic efficiency above 90% at the industrially relevant current density for over 120 h. This work provides a proof of concept of tailored conductive zeolite as a favorable electrocatalytic support for industrial-level CO2 electrolysis and will significantly enhance the adaptability of conductive zeolite-based electrocatalysts in a variety of electrocatalysis and energy conversion applications.

Assessment of Hydrazone Derivatives for Enhanced Steel Corrosion Resistance in 15 wt.% HCl Environments: A Dual Experimental and Theoretical Perspective.

This study evaluates the corrosion inhibition capabilities of two novel hydrazone derivatives, (E)-2-(5-methoxy-2-methyl-1H-indol-3-yl)-N'-(4-methylbenzylidene)acetohydrazide (MeHDZ) and (E)-N'-benzylidene-2-(5-methoxy-2-methyl-1H-indol-3-yl)acetohydrazide (HHDZ), on carbon steel in a 15 wt.% HCl solution. A comprehensive suite of analytical techniques, including gravimetric analysis, potentiodynamic polarization (PDP), electrochemical impedance spectroscopy (EIS), and scanning electron microscopy (SEM), demonstrates their significant inhibition efficiency. At an optimal concentration of 5 × 10-3 mol/L, MeHDZ and HHDZ achieve remarkable inhibition efficiencies of 98% and 94%, respectively. EIS measurements reveal a dramatic reduction in effective double-layer capacitance (from 236.2 to 52.8 and 75.3 µF/cm2), strongly suggesting inhibitor adsorption on the steel surface. This effect is further corroborated by an increase in polarization resistance and a significant decrease in corrosion current density at optimal concentrations. Moreover, these inhibitors demonstrate sustained corrosion mitigation over extended exposure durations and maintain effectiveness even under elevated temperatures, highlighting their potential for diverse operational conditions. The adsorption process of these inhibitors aligns well with the Langmuir adsorption isotherm, implying physicochemical interactions at the carbon steel surface. Density functional tight-binding (DFTB) calculations and molecular dynamics simulations provide insights into the inhibitor-surface interaction mechanism, further elucidating the potential of these hydrazone derivatives as highly effective corrosion inhibitors in acidic environments.

Biochemical and computational inhibition of α-glucosidase by novel metronidazole-linked 1H-1,2,3-triazole and carboxylate moieties: kinetics and dynamic investigations

In the current study, metronidazole derivatives containing 1H-1,2,3-triazole and carboxylate moieties were evaluated in vitro and by computational methods for their anti-diabetic potential to insight into their medicinal use for the management of type II diabetes mellitus. Interestingly all 14 compounds displayed high to significant inhibitory capability against the key carbohydrate’s digestive enzyme α-glucosidase with IC50 values in range of 9.73–56.39 μM, as compared to marketed drug acarbose (IC50 = 873.34 ± 1.67 μM). Compounds 5i and 7c exhibited the highest inhibition, therefore, these two compounds were further evaluated for their mechanistic studies to explore its type of inhibition. Compounds 5i and 7c both displayed a concentration-dependent (competitive type of inhibition) with Ki values 7.14 ± 0.01, 6.15 ± 0.02 μM, respectively, which conclude their favourable interactions with the active site residues of the α-glucosidase. Interestingly all compounds are non-cytotoxic against BJ cell line. To further validate our findings, in-silico approaches like molecular docking, and molecular dynamic simulations were applied to investigate the mode of bindings of compounds with the enzyme and identifies their inhibition mechanism, which strongly complements our experimental findings. Communicated by Ramaswamy H. Sarma

Insights into the corrosion resistance of a novel quinoline derivative on Q235 steel in acidizing medium under hydrodynamic condition: experimental and surface study

Abstract The study concentrated on the fabrication of an environmentally friendly inhibitor, namely ethyl 4-(4-methoxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate derivative of quinoline (MQC), in a single step, and assessed its inhibiting property in highly acidic fluid (15 % HCl) for protecting Q235 steel at 1500 rpm rotation speed. Weight reduction, Potentiodynamic polarization, and electrochemical impedance spectroscopy were utilized in the study to investigate the inhibiting impact of MQC. The estimated findings corroborated the inhibiting data of 93.54 and 98.38 % at 308 K with 100 mg/L/only MQC and MQC + KI/75 mg/L + 0.5 mM, respectively, and the impact of temperature upon the inhibitory capability possessed little impact at larger dose quantities. According to the electrochemical outcomes, the MQC is a mixed-type corrosion inhibitor. The findings of the SEM, EDX, and AFM examinations demonstrated that the MQC established a barrier over the surface of Q235 steel by adsorption, changing the hydrophilic and hydrophobic attributes of the Q235 steel surface. An additional XPS assessment demonstrated MQC molecule adsorption on the Q235 steel surface. Density functional theory (DFT) and molecular dynamic simulations (MD) calculations were further performed to justify the experimental results.

Evaluation of Biological Potency of two Endemic Species Integrated with in vitro and in silico Approches: LC-MS/MS Analysis of the Plants.

In the present study, the main phytochemical components of endemic plant extracts and inhibitory potency were screened related to different biological activities. Seven compounds were quantified, and cyanidin-3-o-glucoside was the dominant secondary metabolite in the extract of plants. The extract from P. asiae-minoris (PAM) exhibited the best enzyme inhibitory activity against BChE (1.73±0.23 μg mL-1 ), tyrosinase (2.47±0.28 μg mL-1 ), α-glucosidase (5.28±0.66 μg mL-1 ), AChE (8.66±0.86 μg mL-1 ), and ACE (19.27±1.02 μg mL-1 ). In vitro antioxidant assay, PAM extract possessed the highest activity in respect of DPPH radical scavenging (24.29±0.23 μg/mL), ABTS⋅+ scavenging (13.50±0.27 μg/mL) and FRAP reducing power (1.56±0.01 μmol TE/g extract). MIC values ranged from 1-8 mg/mL for antibacterial ability, and the PAM extract showed a stronger effect for B. subtilis, E. faecalis, and E. coli at 1 mg/mL. The antiproliferative ability of A. bartinense (AB) extract demonstrated a suppressive effect (IC50 : 70.26 μg/mL) for pancreatic cancer cell lines. According to the affinity scores analysis, the cyanidin-3-o-glucoside demonstrated the lowest docking scores against ACE, AChE, BChE, and collagenase. It was found that the PAM extract exhibited better inhibitory capabilities than A. bartinense. The P. asiae-minoris plant, reported to be in the Critically Endangered (CR) category, should be conserved by culturing, considering its biological abilities.

Characteristics and Antibacterial Activities of Bacteriocin Produced by Lactid Acid Bacteria Isolate LG-50 and LG-90

Biopreservative agents is natural food preservative agent derived from microbes such as bacteriocin produced by lactic acid bacteria (LAB). Bacteriocin is a protein compound that has a small molecular weight and has antibacterial activity because it is effective in preventing the growth of pathogenic bacteria in food and beverages. Escherichia coli and Staphylococcus aureus are pathogenic bacteria that can contaminate seafood products because they can cause infection and food toxication. Isolates LG-50 and LG-90 are LAB, bacterial collection of the Microbiology Laboratory, Faculty of Biology, Isolate from mangrove sediment in Logending beach. Both isolates are not yet known for their potencies to synthesize bacteriocin and its inhibitory capability to the growth E. coli and S. aureus. The research aimed to determine the ability of LG-50 and LG-90 isolates to produce bacteriocin, to determine the ability of LG-50 and LG-90 isolates to inhibit the growth of E. coli and S. aureus bacteria invitro, to identity the characteristics of isolate LG-50 and LG-90 from Logending beach mangrove sediment. The results of this research show that the bacteriocins LG-50 and LG-90 were able to inhibit the growth of E.coli with inhibition zone diameters of 13.5 mm and 13 mm, in S. aureus with inhibition zone diameters of 15 mm and 15.5 mm.

In-vitro endophytic bacteria activity against Ralstonia syzygii subsp. indonesiensis, the causal agent of bacterial wilt disease in tomato (Solanum lycopersicum) to achieve sustainable agriculture

The bacterial wilt disease transmitted through soil, identified as Ralstonia syzygii subsp. indonesiensis, is a substantial vascular disease and major constraint in various Solanaceae plants. The use endophytic bacteria-as Arthrobacter sp. and Bacillus thuringiensis-is one approach to control this pathogen. In vitro test using the disc paper method was conducted to evaluate the compatibility of Arthrobacter sp. and B. thuringiensis, along with their inhibitory capabilities through secondary metabolite production, in suppressing the growth of R. syzygii subsp. indonesiensis. The results showed incompatibility among isolates of endophytic bacterial, consequently, both endophytic bacteria were capable suppressing the growth of the R. syzygii subsp. indonesiensis significantly. Arthrobacter sp. formed a larger inhibition zone compared to B. thuringiensis, and both endophytic bacteria can be candidate biological control agents to reduce pesticide use to control R. syzygii subsp. indonesiensis, which therefore achieving more environmentally agriculture sustainability.

Exploring the antagonist potential of indigenous Trichoderma spp., Bacillus, and Pseudomonas against Phytophthora palmivora of Soe mandarin in East Nusa Tenggara, Indonesia

Phytophthora palmivora-induced root and basal stem rot pose a significant threat to the survival of Soe mandarin plants in East Nusa Tenggara Province, Indonesia. We isolated four Trichoderma species, five Bacillus, and 13 Pseudomonas isolates from the rhizosphere of healthy Soe mandarin. This study pursued two main objectives: (a) assessing the inhibitory capabilities of indigenous Trichoderma spp., Bacillus, and Pseudomonas towards P. palmivora in vitro, and (b) investigating the combined efficacy of Trichoderma spp., Bacillus, and Pseudomonas in controlling P. palmivora in a pot trial. Results revealed that four Trichoderma species (T. asperellum, T. hamatum, T. harzianum, and T. viride) significantly inhibited the growth of P. palmivora. Notably, T. asperellum exhibited the highest inhibition, at 84.31%, followed closely by T. harzianum (84.11%), T. viride (83.67%), and T. hamatum (80.28%). Bacillus and Pseudomonas exhibited varying levels of inhibition to P. palmivora growth in vitro, with the most substantial inhibition observed in Bacillus 1, followed by Pseudomonas 6. In the subsequent pot trial, the application of Trichoderma, Bacillus, or Pseudomonas, either individually or in combination, significantly increased the height increment and reduced the disease incidence caused by P. palmivora in Soe mandarin seedlings.

Plant-derived exosomes extracted from Lycium barbarum L. loaded with isoliquiritigenin to promote spinal cord injury repair based on 3D printed bionic scaffold.

Plant-derived exosomes (PEs) possess an array of therapeutic properties, including antitumor, antiviral, and anti-inflammatory capabilities. They are also implicated in defensive responses to pathogenic attacks. Spinal cord injuries (SCIs) regeneration represents a global medical challenge, with appropriate research concentration on three pivotal domains: neural regeneration promotion, inflammation inhibition, and innovation and application of regenerative scaffolds. Unfortunately, the utilization of PE in SCI therapy remains unexplored. Herein, we isolated PE from the traditional Chinese medicinal herb, Lycium barbarum L. and discovered their inflammatory inhibition and neuronal differentiation promotion capabilities. Compared with exosomes derived from ectomesenchymal stem cells (EMSCs), PE demonstrated a substantial enhancement in neural differentiation. We encapsulated isoliquiritigenin (ISL)-loaded plant-derived exosomes (ISL@PE) from L. barbarum L. within a 3D-printed bionic scaffold. The intricate construct modulated the inflammatory response following SCI, facilitating the restoration of damaged axons and culminating in ameliorated neurological function. This pioneering investigation proposes a novel potential route for insoluble drug delivery via plant exosomes, as well as SCI repair. The institutional animal care and use committee number is UJS-IACUC-2020121602.

Machine Learning Application for Medicinal Chemistry: Colchicine Case, New Structures, and Anticancer Activity Prediction.

In the contemporary era, the exploration of machine learning (ML) has gained widespread attention and is being leveraged to augment traditional methodologies in quantitative structure-activity relationship (QSAR) investigations. The principal objective of this research was to assess the anticancer potential of colchicine-based compounds across five distinct cell lines. This research endeavor ultimately sought to construct ML models proficient in forecasting anticancer activity as quantified by the IC50 value, while concurrently generating innovative colchicine-derived compounds. The resistance index (RI) is computed to evaluate the drug resistance exhibited by LoVo/DX cells relative to LoVo cancer cell lines. Meanwhile, the selectivity index (SI) is computed to determine the potential of a compound to demonstrate superior efficacy against tumor cells compared to its toxicity against normal cells, such as BALB/3T3. We introduce a novel ML system adept at recommending novel chemical structures predicated on known anticancer activity. Our investigation entailed the assessment of inhibitory capabilities across five cell lines, employing predictive models utilizing various algorithms, including random forest, decision tree, support vector machines, k-nearest neighbors, and multiple linear regression. The most proficient model, as determined by quality metrics, was employed to predict the anticancer activity of novel colchicine-based compounds. This methodological approach yielded the establishment of a library encompassing new colchicine-based compounds, each assigned an IC50 value. Additionally, this study resulted in the development of a validated predictive model, capable of reasonably estimating IC50 values based on molecular structure input.

A novel DDIT3 activator dehydroevodiamine effectively inhibits tumor growth and tumor cell stemness in pancreatic cancer

BackgroundThe existence of pancreatic cancer stem cells (PCSCs) results in limited survival benefits from current treatment options. There is a scarcity of effective agents for treating pancreatic cancer patients. Dehydroevodiamine (DeHE), a quinazoline alkaloid isolated from the traditional Chinese herb Evodiae fructus, exhibited potent inhibition of pancreatic ductal adenocarcinoma (PDAC) cell proliferation and tumor growth both in vitro and in vivo. MethodsThe cytotoxic effect of DeHE on PDAC cells was assessed using CCK-8 and colony formation assays. The antitumor efficacy of DeHE were appraised in human PANC-1 xenograft mouse model. Sphere formation assay and flow cytometry were employed to quantify the tumor stemness. RNA‐Seq analysis, drug affinity responsive target stability assay (DARTS), and RNA interference transfection were conducted to elucidate potential signaling pathways. Western blotting and immunohistochemistry were utilized to assess protein expression levels. ResultsDeHE effectively inhibited PDAC cell proliferation and tumor growth in vitro and in vivo, and exhibited a better safety profile compared to the clinical drug gemcitabine (GEM). DeHE inhibited PCSCs, as evidenced by its suppression of self-renewal capabilities of PCSCs, reduced the proportion of ALDH+ cells and downregulated stemness-associated proteins (Nanog, Sox-2, and Oct-4) both in vitro and in vivo. Furthermore, there is potential involvement of DDIT3 and its downstream DDIT3/TRIB3/AKT/mTOR pathway in the suppression of stemness characteristics within DeHE-treated PDAC cells. Additionally, results from the DARTS assay indicated that DeHE interacts with DDIT3, safeguarding it against degradation mediated by pronase. Notably, the inhibitory capabilities of DeHE on PDAC cell proliferation and tumor stemness were partially restored by siDDIT3 or the AKT activator SC-79. ConclusionIn summary, our study has identified DeHE, a novel antitumor natural product, as an activator of DDIT3 with the ability to suppress the AKT/mTOR pathway. This pathway is intricately linked to tumor cell proliferation and stemness characteristics in PDAC. These findings suggest that DeHE holds potential as a promising candidate for the development of innovative anticancer therapeutics.

Exploring the potency of diazo-coumarin containing hybrid molecules: Selective inhibition of tumor-associated carbonic anhydrase isoforms IX and XII.

This study introduces a series of ten hybrid molecules DK(1-10), which combine diazo and coumarin moieties along with diverse aromatic substitutions. The primary objective was to evaluate the inhibitory capabilities of these compounds against four prominent isoforms: the cytosolic hCA I and II, as well as the tumor-associated membrane-bound hCA IX and XII. Impressively, the majority of the tested compounds exhibited significant inhibition activity against the tumor-associated isoforms hCA IX and XII, with KI values ranging from 29.2 to 293.3 nM. Notably, compound DK-8 displayed particularly robust inhibitory activity against the tumor-associated membrane-bound isoforms, hCA IX and XII, yielding KI values of 32.5 and 29.2 nM, respectively. Additionally, another derivative, DK-9, containing a primary sulfonamide, exhibited notable inhibition against hCA XII with a KI value of 36.4 nM. This investigation aimed to explore the structure-activity relationships within these compounds, shedding light on how various substitutions and structural components influence their inhibitory potential. As a result, these compounds present promising candidates for further exploration in medicinal and pharmacological research. Their ability to selectively inhibit specific isoforms, particularly those associated with hypoxic tumors, suggests their potential as foundational compounds for the development of novel therapeutic agents.

Unveiling the influence of furan and thiophene on the corrosion inhibition capabilities of novel hydrazones derivatives in carbon steel/HCl interface: A dual experimental-theoretical study

The use of corrosion inhibitors is a critical measure in the preservation of metals. In this research, the performance of two hydrazone derivatives, N′-[(E)-furan-2-ylmethylidene]− 2-(6-methoxynaphthalen-2-yl)propanehydrazide (NFH) and 2-(6-methoxynaphthalen-2-yl)-N′-[(E)-thiophen-2-ylmethylidene]propanehydrazide (NTH), was evaluated for their ability to inhibit corrosion of carbon steel in a 1.0 mol/L HCl solution. Electrochemical Impedance Spectroscopy (EIS), Potentiodynamic Polarization (PDP), and Scanning Electron Microscopy with Energy-Dispersive X-ray Spectroscopy (SEM-EDX) were employed to assess the compounds' inhibition performance. The experimental results demonstrated that the efficiency of the inhibitors improved with increasing concentration. NFH reached a 90% threshold, while NTH peaked at 93%. This superior performance of NTH was attributed to its thiophene group, in contrast to the furan moiety in NFH. PDP data revealed that both compounds acted as mixed inhibitors, inhibiting both anodic and cathodic reactions. The EIS results indicated a significant increase in polarization resistance, accompanied by a reduction in the values of effective double-layer capacitance, due to the adsorption of inhibitor molecules. The adsorption of inhibitor molecules conformed to the Langmuir isotherm model, suggesting a combined physicochemical mode of interactions with the carbon steel, which was corroborated by potential of zero charge (PZC) analysis. SEM-EDX analysis confirmed the thiazole derivatives' capacity to protect the metal against corrosion. Quantum Chemical Calculations (QCCs) along with Molecular Dynamics (MD) simulations elucidated the reactivity descriptors and the optimal adsorption configurations on the Fe(110) surface. This exploration underscores the significance of the thiophene moiety in enhancing the adsorptive and corrosion inhibitory properties of the hydrazones, thus providing strategic insights for their future refinement and application.

Enhancement of anti-microbial corrosion properties through coatings incorporating S2− responsive TCS-MSNs@TA-FeIII nanofillers

In environments susceptible to microbiologically influenced corrosion (MIC), conventional coatings frequently lack antimicrobial properties, resulting in diminished corrosion protection. The direct incorporation of antimicrobial agents into coatings may lead to continuous leakage. In this study, we tackled this challenge by utilizing smart nanofillers known as TCS-MSNs@TA-FeIII, which form mesoporous silica nanoparticles (MSNs) encapsulated by tannic acid-Fe3+ and loaded with triclosan (TCS). These nanofillers exhibited responsiveness to variations in S2− concentration caused by sulfate-reducing bacteria's (SRB) metabolic activities, enabling controlled release of TCS within the low S2− concentration range of 0.05 to 3 mM. Additionally, we evaluated the antimicrobial and anti-corrosion properties of the coating after integrating it into a water-based epoxy coating within an SRB environment. The results showcased exceptional performance of the TCS-MSNs@TA-FeIII coating, characterized by the highest impedance modulus (3.19 × 106 Ω·cm2), lowest corrosion current density (2.04 × 10−8 A·cm−2), and remarkable antimicrobial efficacy. This study offers valuable insights into developing novel coatings with enduring MIC inhibition capabilities while also broadening the potential application range of organic coatings.

Identification of cyclooxygenase-II inhibitory saponins from fenugreek wastes: Insights from liquid chromatography-tandem mass spectrometry metabolomics, molecular networking, and molecular docking.

This research explores sustainable applications for waste generated from fenugreek (Trigonella foenum-graecum), a plant with both nutritional and medicinal uses. The study specifically targets waste components as potential sources of nutrients and bioactive compounds. The focus is to conduct detailed metabolic profiling of fenugreek waste, assess its anti-inflammatory properties by studying its cyclooxygenase (COX) inhibitory effect, and correlate this effect to the metabolite fingerprint. Ethanolic extracts of fenugreek fruit pericarp and a combination of leaves and stems were subjected to untargeted metabolic profiling using liquid chromatography-mass spectrometry integrated with online database searches and molecular networking as an effective dereplication strategy. The study also scrutinized the COX inhibitory capabilities of these extracts and saponin-rich fractions prepared therefrom. Molecular docking was employed to investigate the specific interactions between the identified saponins and COX enzymes. The analysis led to the annotation of 81 metabolites, among which saponins were predominant. The saponin-rich fraction of the fruit pericarp extract displayed the strongest COX-II inhibitory activity in the in vitro inhibition assay (IC50 value of 81.64 ± 3.98 μg/mL). The molecular docking study supported the selectivity of the identified saponins towards COX-II. The two major identified saponins, namely, proto-yamogenin 3-O-[deoxyhexosyl (1 → 2)] [hexosyl (1 → 4)] hexoside 26-O-hexoside and trigofenoside A, were predicted to have the highest affinity to the COX-II receptor site. In the present study, we focused on the identification of COX-II inhibitory saponins in fenugreek waste through an integrated approach. The findings offer valuable insights into potential anti-inflammatory and cancer chemoprotective applications of fenugreek waste.

Hydroxylated Tetramethoxyflavone Affects Intestinal Cell Permeability and Inhibits Cytochrome P450 Enzymes.

Tetramethoxyflavones (TMFs) found in the Citrus genus have garnered considerable interest from food scientists and the health food industry because of their promising biological properties. Nonetheless, there are currently limited data available regarding the effectiveness and bioavailability of "hydroxylated TMFs", which are flavones known for their potential in disease prevention through dietary means. This study aims to provide insights into the chemical and biological properties of hydroxylated TMF and evaluates its effects on intestinal cell permeability and cytochrome P450 (CYP) inhibition. Liquid chromatography-mass spectrometry (LC-MS) and microsomes analyze the TMFs and hydroxylated TMFs, elucidating cell penetration and metabolic inhibition potential. 3H7-TMF shows the fastest (1-h) transport efficiency in intestinal cells. The Caco-2 cell model exhibits significant transport and absorption efficiency. Dissolved hydroxyl-TMF with hydrophilicity possibly permeates the gut. 3H7-TMF has higher transport efficiency (46%) 3H6-TMF (39%). IC50 values of TMFs (78-TMF, 57-TMF, 3H7-TMF, 3H6-TMF) against CYP enzymes (CYP1A2, CYP2D6, CYP2C9, CYP2C19, CYP3A4) range from 0.15 to 108 μM, indicating potent inhibition. Hydroxyl groups enhance TMF hydrophilicity and membrane permeability. TMFs display varied inhibitory effects due to hydroxyl and methoxy hindrance. This study underscores the strong CYP inhibitory capabilities in these TMFs, implying potential food-drug interactions if used in medicines or supplements. These findings can also help with food nutrition improvement and pharma food developments through innovative approaches for Citrus waste valorization.

Inhibition of Pseudomonas aeruginosa quorum sensing by chemical induction of the MexEF-oprN efflux pump.

The cell-to-cell communication system quorum sensing (QS), used by various pathogenic bacteria to synchronize gene expression and increase host invasion potentials, is studied as a potential target for persistent infection control. To search for novel molecules targeting the QS system in the Gram-negative opportunistic pathogen Pseudomonas aeruginosa, a chemical library consisting of 3,280 small compounds from LifeArc was screened. A series of 10 conjugated phenones that have not previously been reported to target bacteria were identified as inhibitors of QS in P. aeruginosa. Two lead compounds (ethylthio enynone and propylthio enynone) were re-synthesized for verification of activity and further elucidation of the mode of action. The isomeric pure Z-ethylthio enynone was used for RNA sequencing, revealing a strong inhibitor of QS-regulated genes, and the QS-regulated virulence factors rhamnolipid and pyocyanin were significantly decreased by treatment with the compounds. A transposon mutagenesis screen performed in a newly constructed lasB-gfp monitor strain identified the target of Z-ethylthio enynone in P. aeruginosa to be the MexEF-OprN efflux pump, which was further established using defined mex knockout mutants. Our data indicate that the QS inhibitory capabilities of Z-ethylthio enynone were caused by the drainage of intracellular signal molecules as a response to chemical-induced stimulation of the MexEF-oprN efflux pump, thereby inhibiting the autogenerated positive feedback and its enhanced signal-molecule synthesis.