Computational assessment of natural compounds as potential hexokinase 2 inhibitors.

Hexokinase 2 (HK2), a central enzyme in the glycolytic pathway, is frequently overexpressed in malignant cells, contributing to enhanced glucose metabolism and tumor progression. Despite its recognized role in cancer metabolism, effective and selective HK2 inhibitors from natural sources remain underexplored. This study aimed to identify promising natural product inhibitors of HK2 through an integrated computational approach.

Corrigendum to "Ultrasound assisted deep eutectic solvent-based extraction of Montepulciano d' Abruzzo grape seeds for the recovery of the grape seed oil and its biological evaluation" [Food Chemistry: X 26 (2025) 1-8/102273].

[This corrects the article DOI: 10.1016/j.fochx.

and as Health Promoting Nutraceuticals: Assessing Their Role Combining In Vitro In Silico and Chemical Approaches.

species are known for their ability to produce multiple classes of secondary metabolite and in this article the possible health-promoting role of and have been evaluated combining in vitro and in silico approaches. and extracts were obtained using different solvents (ethyl acetate, aceton, aceton/water, and water) and the composition was compared using NMR and LC-MS based approaches. Myricetin-3--glucoside, Kaemempferol -3--glucoside, and hyperopliphylirrin were present only in Rutin, quercetin-3--rhamnoside ant the triterpenoids oleanolic and ursolic acid were only detected in .

Ultrasound assisted deep eutectic solvent-based extraction of Montepulciano d' Abruzzo grape seeds for the recovery of the grape seed oil and its biological evaluation.

Grape seeds are by-products of vinification process. In this work, a green ultrasound-assisted extraction of grape seeds oil was performed by using the natural volatile deep eutectic solvent (NADES) menthol: thymol 1:1. The obtained oil was compared to that deriving from UAE with -hexane in terms of fatty acids composition and biological activities.

Development of linear β-turn inducers containing peptides as arc mimetics with DNA topological and sequence selectivity.

In general, biological macromolecules such as proteins interact with the major groove of the ds-DNA via hydrogen bonds formation, thus blocking the site access of TFs to specific DNA sequences. Considering that the primary sequence of arc repressor responsible for DNA binding is well-characterized as well as the 3D-conformational requisites for its optimal interactions with the specific DNA base-pairs, a series of well-tailored arc analogues could be designed using computational molecular tools and available structural data. These novel molecular entities have been synthesized following ultrasound assisted-solid phase peptide synthesis (US-SPPS), characterized by NMR experiments and screened for TAGA box selectivity on DNA oligomers using a battery of DNA displacement assays.

Azobenzene as Multi-Targeted Scaffold in Medicinal Chemistry.

The discovery of a multi-target scaffold in medicinal chemistry is an important goal for the development of new drugs with different biological effects. Azobenzene is one of the frameworks in medicinal chemistry used for its simple synthetic methods and for the possibility to obtain a great variety of derivatives by simple chemical modifications or substitutions. Phenyldiazenyl-containing compounds show a wide spectrum of pharmacological activities, such as antimicrobial, anti-inflammatory, anti-neurodegenerative, anti-cancer, and anti-enzymatic.

Elucidation on the In Vivo Activity of the Bivalent Opioid Peptide MACE2 against Several Types of Chronic Pain.

Biphalin is a bivalent μ/δ opioid receptor agonist showing a promising therapeutic profile with reduced side effects, but as a peptide is limited by poor metabolic stability and blood-brain barrier penetration. To improve these features, we developed the ligand and showed initial in vivo efficacy. To further explore the druggability of this ligand, in this report, we tested metabolic stability in human plasma, receptor engagement by 3 different routes of administration using the tail-flick test, and efficacy in 2 different pathological and chronic pain models.

Valorization of grape pomace extracts against cranberry, elderberry, rose hip berry, goji berry and raisin extracts: Phytochemical profile and in vitro biological activity.

The circular economy is gaining attention around the world as a sustainable approach to tackling environmental problems, promoting more responsible management of resources. The aim of this work is the valorization of grape pomace as a waste product of agrifood chain. We prepared decoction (DC), ultrasound-assisted and microwave-assisted extracts (UAE and MAE respectively) of grape pomace, determining their phytochemical profile (using HPLC-ESI-Q-TOF-MS), antioxidant activity and enzyme inhibitory effects.

Treatment expectations and clinical outcomes following repetitive transcranial magnetic stimulation for treatment-resistant depression.

Background: Patient expectations, including both positive (placebo) and negative (nocebo) effects, influence treatment outcomes, yet their impact on acute repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) is unclear.

Methods: In this single-center retrospective chart review, 208 TRD patients completed the Stanford Expectation of Treatment Scale (SETS) before starting open-label rTMS treatment. Patients were offered two excitatory rTMS protocols (deep TMS or intermittent theta-burst stimulation), which stimulated the left dorsolateral prefrontal cortex.

Influence of extraction solvents on the chemical constituents and biological activities of Astragalus aduncus from Turkey flora: In vitro and in silico insights.

The n-hexane, ethyl acetate, ethanol, ethanol/water (70% ethanol), and water extracts of Astragalus aduncus aerial parts were investigated for their antioxidant potential, enzyme inhibition activity (anti-acetylcholinesterase [AChE], anti-butyrylcholinesterase [BChE], antityrosinase, antiamylase, and antiglucosidase) and antiproliferative effect (against colon adenocarcinoma cell line [HT-29], gastric cancer cell line [HGC-27], prostate carcinoma cell line [DU-145], breast adenocarcinoma cell line [MDA-MB-231], and cervix adenocarcinoma cell line [HeLa]). In addition, the phytochemical profile of the extracts was evaluated using validated spectrophotometric and high-pressure liquid chromatography-electrospray ionization/tandem mass spectroscopy methods. Generally, the 70% ethanol extract demonstrated the strongest antioxidant properties, and it was the richest source of total phenolic constituents.

A New Culture Medium Rich in Phenols Used for Screening Bitter Degrading Strains of Lactic Acid Bacteria to Employ in Table Olive Production.

The olive oil industry recently introduced a novel multi-phase decanter with the "Leopard DMF" series, which gives a by-product called pâté, made up of pulp and olive wastewater with a high content of phenolic substances and without pits. This study aims to create a new culture medium, the Olive Juice Broth (OJB), from DMF pâté, and apply it to select bacteria strains able to survive and degrade the bitter substances normally present in the olive fruit. Thirty-five different bacterial strains of from the CREA-IT.

In Vitro and In Vivo Pharmacological Profiles of LENART01, a Dermorphin-Ranatensin Hybrid Peptide.

Diverse chemical and pharmacological strategies are currently being explored to minimize the unwanted side effects of currently used opioid analgesics while achieving effective pain relief. The use of multitarget ligands with activity at more than one receptor represents a promising therapeutic approach. We recently reported a bifunctional peptide-based hybrid LENART01 combining dermorphin and ranatensin pharmacophores, which displays activity to the mu-opioid receptor (MOR) and dopamine D2 receptor (D2R) in rat brains and spinal cords.

Chemical exploration of different extracts from leaves and their potential utilization for global health problems: and network pharmacology validation.

L. is of great interest as a traditional additive in various folk remedies in several countries, including Turkey. We aimed to determine the chemical profile (assisted by high-Performance liquid chromatography-electrospray ionization-tandem mass apectrometry (HPLC-ESI-MS/MS) experiments of three extracts obtained by different polarity solvents viz.

Therapeutic Effect of an Ursolic Acid-Based Nutraceutical on Neuronal Regeneration after Sciatic Nerve Injury.

Peripheral nerve injuries lead to severe functional impairments and long recovery times, with limited effectiveness and accessibility of current treatments. This has increased interest in natural bioactive compounds, such as ursolic acid (UA). Our study evaluated the effect of an oleolyte rich in UA from white grape pomace (WGPO) on neuronal regeneration in mice with induced sciatic nerve resection, administered concurrently with the induced damage (the WGPO group) and 10 days prior (the PRE-WGPO group).

Opioid/Dopamine Receptor Binding Studies, NMR and Molecular Dynamics Simulation of LENART01 Chimera, an Opioid-Bombesin-like Peptide.

The design and development of hybrid compounds as a new class of drug candidates remains an excellent opportunity to improve the pharmacological properties of drugs (including enzymatic stability, efficacy and pharmacokinetic and pharmacodynamic profiles). In addition, considering various complex diseases and/or disorders, the conjugate chemistry approach is highly acceptable and justified. Opioids have long been recognized as the most potent analgesics and serve as the basic pharmacophore for potent hybrid compounds that may be useful in pain management.

New Teixobactin Analogues with a Total Lactam Ring.

Teixobactin is a new antibiotic peptide with strong efficacy against several Gram-positive resistant bacteria, the structure of which is extremely difficult to obtain in the laboratory via multistep conventional synthesis. To face the increasing antibiotic resistant bacteria, it is fundamental to introduce new types of antibiotics with innovative mechanisms of action without resistance; thus, many scientists are studying and developing new methods to synthesize teixobactin analogues. In this work, seven Arg-teixobactin analogues with a total lactam ring have been prepared via solid phase peptide synthesis.

The Effect of Washing, Blanching and Frozen Storage on Pesticide Residue in Spinach.

Spinach ( L.) is a representative green leafy vegetable commonly consumed fresh or as a ready-to-cook frozen product, with increasing consumption because of its many health-related properties. Among leafy vegetables, spinach poses a major concern in terms of pesticide residue detection due to common phytotechnical practices.

Evaluation of Antimicrobial Activities against Various Strains of a Novel Hybrid Peptide-LENART01.

Finding the ideal antimicrobial drug with improved efficacy and a safety profile that eliminates antibiotic resistance caused by pathogens remains a difficult task. Indeed, there is an urgent need for innovation in the design and development of a microbial inhibitor. Given that many promising antimicrobial peptides with excellent broad-spectrum antibacterial properties are secreted by some frog species (e.

Understanding the Chemical Composition and Biological Activities of Different Extracts of Leaves: A Potential Source of Bioactive Compounds for the Food Industry.

(Roem. & Schult.) K.

Placebo Effects and Neuromodulation: Ethical Considerations and Recommendations.

Placebo-controlled trials are the gold standard of evaluating treatment efficacy in clinical research. Neuromodulation is emerging as an important treatment pathway for many neuropsychiatric conditions, and placebo control arms of these trials require careful design with unique considerations (e.g.

Rimonabant-Based Compounds Bearing Hydrophobic Amino Acid Derivatives as Cannabinoid Receptor Subtype 1 Ligands.

In this study, 1-pyrazole-3-carboxylic acids related to the cannabinoid type 1 (CB1) receptor antagonist rimonabant were amidated with valine or -leucine, and the resulting acids were further diversified as methyl esters, amides, and -methyl amides. receptor binding and functional assays demonstrated a wide series of activities related to the CB1 receptors (CB1Rs). Compound showed a high CB1R binding affinity ( = 6.

Food-inspired peptides from spinach Rubisco endowed with antioxidant, antinociceptive and anti-inflammatory properties.

Rubiscolin-6 (amino acid sequence: YPLDLF) is a selective δ-opioid receptor peptide isolated from spinach Rubisco. Its synthetic analogue, peptide YPMDIV is the most potent described so far for its increased opioid activity, thus in this work it was considered as for the design of twelve new analogues . Firstly all the novel compounds have been tested for their antinociceptive and anti-inflammatory capacity and in order to evaluate their ability to maintain or loss the original activity.

The Evanescent Bouquet of Individual Bear Fingerprint.

The evanescent and invisible communication carried by chemical signals, pheromones, or signature mixtures or, as we prefer, the pheromonal individual fingerprint, between members of the same species is poorly studied in mammals, mainly because of the lack of identification of the molecules. The difference between pheromones and the pheromonal individual fingerprint is that the former generate stereotyped innate responses while the latter requires learning, i.e.

Design of Analgesic Trivalent Peptides with Low Withdrawal Symptoms: Probing the Antinociceptive Profile of Novel Linear and Cyclic Peptides as Opioid Pan Ligands.

The discovery of efficacious and safe analgesics with reduced side effects is the foremost challenge in the pain field. In this work, we report the and evaluation of linear and cyclic analogues of biphalin with the aim to complete the series of structural modifications previously applied in the development of opioid peptides incorporating a xylene bridge. Replacement of Tyr by Dmt (2,5-dimethyltyrosine) in the linear biphalin analogue and cyclic analogue resulted in two new compounds (namely, and ) endowed with improved KOR/MOR/DOR binding affinity.