Search Results (262)

Background/Objectives: This study focused on synthesizing novel alkenyl derivatives of azinylferrocenes and evaluating their potential as Alzheimer’s disease (AD) therapeutics. Methods: 1-Azinyl-1′-acetylferrocenes were obtained by regioselective acetylation of azinylferrocenes, followed by the Wittig reaction or reduction of 1-azinyl-1′-acetylferrocenes and subsequent dehydration of the resulting alcohols. The synthesized compounds underwent the following biological activity testing relevant to AD: inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and off-target carboxylesterase (CES); antioxidant capacity (ABTS and FRAP assays); inhibition of Aβ₄₂ self-aggregation (thioflavin method); blocking AChE-induced β-amyloid aggregation (propidium displacement); and cytotoxicity in SH-SY5Y and MSC-Neu cells (MTT assay). Results: Quinoline and bipyridine derivatives demonstrated effective cholinesterase inhibition, especially quinoline 7b (AChE IC₅₀ 3.32 μM; BChE IC₅₀ 3.68 μM), while acridine derivatives were poor inhibitors. Quantum chemical (QC) calculations predicted that acridine derivatives were especially prone to form stable dimers. Molecular docking into protein targets generated by an AlphaFold3 reproduction code showed that these dimers were too bulky to access enzyme active sites, yet they could bind to protein surfaces to inhibit Aβ₄₂ self-aggregation and displace propidium from the AChE peripheral anionic site. All compounds showed high antioxidant activity in ABTS and FRAP assays, with quinoline derivatives being 2–4 times more potent than Trolox. QC calculations supported these findings. Quinoline and bipyridine derivatives also exhibited low cytotoxicity and scant CES inhibition. Conclusions: Overall, the synthesized ferrocenes, particularly the quinoline and bipyridine derivatives, appear promising for further research as multifunctional therapeutic agents targeting AD due to their anticholinesterase, antiaggregating, and antioxidant activities combined with low toxicity. Full article

Background: Aromatic plants like peppermint (Mentha x piperita, Lamiaceae) have a long tradition of use. Most of the plant material is used to produce herbal drugs and for the isolation of essential oils. However, since essential oils are present in very small amounts, the largest proportion of plants remains unused. Objectives: The aims of this study were the analysis of chemical, biochemical, antimicrobial, and pharmacological properties of peppermint waste material extracts (derived from stems, post-distillation waste, and deodorized leaves) in comparison with the officially prepared extract. Results: The obtained results revealed that the investigated peppermint waste extracts (PWEs) are a rich source of phenolic compounds, where rosmarinic acid was determined as the dominant one (7.05–21.19 mg/g d.e.). Antioxidant potential and hepatoprotective effect of PWE were comparable with the official extract, where the most active ones were those prepared by treating the deodorized leaves with both 45% and 75% ethanol. In addition, PWE exhibited notable antimicrobial and anticholinesterase activity. Results of pharmacological studies on experimental animals showed that peppermint extracts (official and those made from deodorized leaves) did not interfere with the effect of the tested drugs, midazolam and fluoxetine. The examined extracts neither exerted an influence on motor coordination nor acted as antidepressants. Results of the elevated plus maze test indicated that PWE affected the activity of the central nervous system. Conclusions: PWEs represent a significant source of phenolic compounds, especially rosmarinic acid, and they can be used in the pharmaceutical industry to produce various herbal products and in the food industry as natural additives. Full article

Teleost fish are the first evolutionary group to exhibit an innate and adaptive immune system. Within the mechanisms of adaptive immunity, fish possess, among others, T-helper cells (CD4-like) and their differentiation machinery, regulated by the master transcription factors T-bet, GATA3, Foxp3, and RORγ. Many studies support the existence of a non-neuronal cholinergic system involved in the immune response, named after the ability of leukocytes to synthesize de novo acetylcholine (ACh). Organophosphorus pesticides (OPs), such as diazoxon (DXN), are examples of compounds that act as cholinergic disruptors with immunotoxic effects. The present study aimed to evaluate the expression of transcription factors in leukocytes (spleen mononuclear cells, SMNCs) of Nile tilapia by modulating cholinergic pathways in immune cells using agonists, antagonists, and diazoxon (DXN), an anticholinesterase substance. The obtained data showed a significant increase in RORγ mRNA expression upon stimulation with the nicotinic agonist, whereas activation of the muscarinic receptor with its agonist increased T-bet mRNA expression. An alteration in RORγ expression levels induced by DXN exposure was also observed. The results suggest a probable directing of the immune response towards a pro-inflammatory profile orchestrated mainly by RORγ and T-bet transcription factors in response to cholinergic stimuli. Full article

Gmelina philippensis Cham. (Lamiaceae) is a traditionally valued medicinal plant with unexplored potential for the management of neurodegenerative disorders. In the present study, the phytochemical profile of its methanolic leaf extract was comprehensively characterized using untargeted liquid chromatography–tandem mass spectrometry metabolomics (LC–MS/MS) and molecular networking. In addition, the extract was evaluated for its antioxidant and cholinesterase inhibitory activities relevant to Alzheimer’s disease (AD). Metabolite profiling led to the annotation of 27 compounds, with a predominance of flavonoids and iridoid glycosides unique to the genus Gmelina, along with phenolic acids, lipids, and other minor compounds. The extract exhibited potent in vitro antioxidant activity, with an IC₅₀ of 7.49 ± 0.002 μg/mL in the DPPH assay and 639.63 ± 0.814 μg AAE/mg in the FRAP assay. Notably, the extract showed significant inhibitory activity against acetylcholinesterase and butyrylcholinesterase, with an IC₅₀ of 4.87 ± 0.16 and 40.99 ± 0.03 μg/mL, respectively. Molecular networking further supported the metabolite annotation and highlighted clusters of bioactive iridoids and flavonoids. Overall, these findings highlight that G. philippensis as a rich source of multi-target bioactive compounds, supporting that the extract has good anti-acetylcholinesterase activity comparable to the rivastigmine that used in neurodegenerative disease. This study provides a promising foundation for the development of novel therapeutic approaches targeting neurodegenerative diseases. Full article

Alzheimer’s disease continues to be one of the most urgent neurodegenerative conditions, with acetylcholinesterase (AChE) inhibitors serving as a fundamental component of contemporary treatment approaches. Growing evidence underscores that marine ecosystems are a rich source of structurally varied and biologically active natural products exhibiting anticholinesterase properties. This review presents a thorough synthesis of marine-derived metabolites—including those sourced from bacteria, fungi, sponges, algae, and other marine life—that demonstrate inhibitory effects against AChE and butyrylcholinesterase (BuChE). Numerous compounds, such as meroterpenoids, alkaloids, peptides, and phlorotannins, not only show nanomolar to micromolar inhibitory activity but also reveal additional neuroprotective characteristics, including antioxidant effects, anti-amyloid properties, and modulation of neuronal survival pathways. Despite these encouraging findings, the transition to clinical applications is hindered by a lack of comprehensive pharmacokinetic, toxicity, and long-term efficacy studies. The structural variety of marine metabolites provides valuable frameworks for the development of next-generation cholinesterase inhibitors. Further interdisciplinary research is essential to enhance their therapeutic potential and facilitate their incorporation into strategies for addressing Alzheimer’s disease and related conditions. Full article

Essential oils from the genus Piper are recognized for their chemical diversity and biological potential, yet Piper platylobum has been scarcely investigated. This study aimed to characterize the chemical composition of the leaf essential oil of P. platylobum and evaluate its antimicrobial, antioxidant, and anticholinesterase activities. The oil was obtained by steam distillation and analyzed through gas chromatography–mass spectrometry (GC-MS) and gas chromatography equipped with a flame ionization detector (GC-FID), leading to the identification of 35 compounds that accounted for 91.11% of the volatile fraction. Dillapiole (42.0%) was the principal constituent, followed by α-(E)-bergamotene (5.69%), (E)-caryophyllene (5.01%), and (E)-isocroweacin (3.75%). Biological assays revealed selective antimicrobial activity, with inhibition observed only against Enterococcus faecium (MIC = 1000 µg/mL), while no effect was detected against other bacterial or fungal strains tested. Antioxidant evaluation showed moderate activity in the ABTS assay (SC₅₀ = 335.71 ± 1.43 µg/mL; TEAC = 45.85 ± 1.68 µM Trolox/g EO), but no activity in the DPPH assay. The essential oil also displayed moderate inhibition of acetylcholinesterase (IC₅₀ = 76.86 ± 1.00 µg/mL), suggesting a potential role in neuroprotective applications. This study constitutes the first report on the chemical composition and biological activities of P. platylabum essential oil, highlighting its potential as a novel source of bioactive compounds. Full article

Background/Objectives: Neurological and psychiatric disorders share overlapping mechanisms, such as oxidative stress, neuroinflammation, and neurotransmitter imbalance. In this context, multitarget natural molecules have gained attention. 1-nitro-2-phenylethane (1N2PE), a major constituent of Aniba canelilla essential oil, is known for its antioxidant, anti-inflammatory, and anticholinesterase effects, yet its neuropharmacological profile remains poorly understood. Methods: This study integrated in silico predictions and in vivo behavioral assays to characterize 1N2PE. Results: Pharmacokinetic analyses indicated favorable drug-like properties, with high gastrointestinal absorption, blood–brain barrier penetration, and no P-gp substrate profile. Molecular docking and dynamics revealed stable interactions with dopamine transporter (DAT, ΔG = −26.26 kcal/mol), prostaglandin-H synthase-1 (PGHS-1, ΔG = −20.27 kcal/mol), serotonin transporter (SERT, ΔG = −18.20 kcal/mol), and acetylcholinesterase (AChE, ΔG = −16.58 kcal/mol). In vivo, using a scopolamine-induced impairment model, 1N2PE significantly improved spatial memory and cognition in the Morris water maze. Treated animals reduced the distance to the target zone by ~40% compared with scopolamine-only rats (p < 0.01), normalized latency during training, and exhibited 30% less immobility (p < 0.05), indicating antidepressant-like effects. Moreover, 1N2PE attenuated anxiety-like thigmotaxis, restoring exploratory patterns (p < 0.0001). Conclusions: Together, these findings highlight 1N2PE as a multitarget candidate for cognitive and psychiatric disorders, combining favorable pharmacokinetic properties with preclinical efficacy, warranting further biochemical and translational investigations. Full article

Background/Objectives: Alzheimer’s disease (AD) is the most prevalent form of dementia and is characterized by a decline in cognition that may be due, in part, to deficient cholinergic signalling. Cholinesterase inhibitors (ChEIs) are the first-line pharmacotherapies for treating the diminished cholinergic function in AD patients. Plant phytochemicals may provide useful ChEIs and mitigate other elements of AD pathology, including oxidative stress. Methods: Herein, the phytochemicals present in Moringa oleifera aqueous and methanolic extracts were identified by LC-MS/MS and the potential of several phytochemicals (4-O-caffeoylquinic acid (4-CQA), quercetin 3-β-D-glucoside (Q3-β-D), chlorogenic acid (CGA), and rutin) to act as ChEIs and antioxidants was assessed. Results: The phytochemicals inhibited human acetylcholinesterase (AChE) in the following order of potency: 4-CQA > Q3-β-D > CGA > rutin; for AChE from Electrophorus electricus, the order of potency was Q3-β-D > 4-CQA > CGA > rutin. For human butyrylcholinesterase (hBuChE), the order of potency was rutin > 4-CQA > Q3-β-D > CGA and for equine serum BuChE, it was 4-CQA > Q3-β-D > rutin > CGA. Molecular docking validated the binding of the phytochemicals to cholinesterases, with binding affinities comparable to or higher than those of ChEI drugs. All the phytochemicals displayed potent radical-scavenging and antioxidant activities across six assays. 4-CQA was the most effective antioxidant in three of the assays. Conclusions: M. oleifera contains phytochemicals with weak ChEI activity and potent antioxidant capacity, with potential use as nutraceuticals to treat the cholinergic signalling deficit and oxidative stress that typifies AD pathology. Full article

Apigenin (AP) is a natural flavonoid with senomorphic potential and neuroprotective action; however, poor aqueous solubility (<1 μg/mL) limits its bioavailability and therapeutic use. Therefore, the aim of this study was to obtain an amorphous dispersion of AP and evaluate its biological properties. Screening of AP solubilization capabilities under supercritical carbon dioxide processing conditions showed that the system with Soluplus (SOL) achieved the greatest improvement in AP dissolution (6455.4 ± 27.2 μg/mL). Using optimized process parameters (50 °C, 6500 PSI), the AP solubility increased to 8050.2 ± 35.1 μg/mL. X-ray powder diffraction (XRPD) confirmed amorphization, aligning with improved dissolution of AP in both acidic and neutral pH media. As a result, using the PAMPA model, an improvement in AP penetration through membranes simulating gastrointestinal and blood–brain barriers was demonstrated. The significant stability of the obtained amorphous AP dispersion (12 months at room conditions) was associated with stabilizing AP–solubilizer intermolecular interactions, mainly expressed as the shifts in the bands of AP in the range of 1018–1269 cm⁻¹ observed in ATR-FT-IR spectra. Chromatographic analysis confirmed the lack of AP decomposition immediately after the preparation of the amorphous dispersion, as well as after 12 months. As expected, the improvement of AP solubility is correlated with better biological activity assessed in selected in vitro tests such as antioxidant properties (2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and cupric ion reducing antioxidant capacity (CUPRAC) assays) and anticholinesterase inhibition capabilities (AChE and BChE assays). The effect of the studies on improving AP solubility under supercritical carbon dioxide processing conditions is obtaining a stable amorphous AP dispersion (up to 12 months). Regardless of the pH of the media, an improvement in AP dissolution and penetration, conditioned by the passive diffusion process, through biological membranes was noted. Moreover, a more efficient antioxidant and neuroprotective effect of AP in the developed amorphous dispersion can also be suggested. Full article

In this study, extraction conditions were optimized to maximize the biological activities of extracts obtained from Paralepista flaccida, an edible mushroom species. Extraction processes were carried out using an ultrasonically assisted system, and two different optimization approaches were used as follows: Response Surface Methodology (RSM) and Artificial Neural Network–Genetic Algorithm (ANN-GA). The antioxidant potentials of the optimized extracts were evaluated using DPPH, FRAP, TAS, TOS, and OSI parameters; anticholinesterase activities were measured against AChE and BChE enzymes; and antiproliferative activities were investigated in A549, MCF-7, and DU-145 human cancer cell lines. In addition, phenolic contents were determined by LC-MS/MS analysis. The findings revealed that the extracts obtained by the RSM method exhibited a superior biological profile compared to ANN-GA extracts in terms of antioxidant, anticholinesterase, and antiproliferative activities. The high cytotoxicity observed, particularly in the MCF-7 line, supports the anticancer potential of this extract. These results demonstrate that optimization strategies are crucial for increasing not only extract yield but also biological functionality. Full article

Background/Objectives: There is evidence concerning herbal medicines and plant-based compounds, including Lamiaceae species, as putative senolytic agents; however, there are only a few reports on Ocimum americanum properties using rat models. The aim of this study was to investigate the neuroprotective effects and potential modes of action of Ocimum americanum L. using ex vivo and in vivo assays to assess the effects of OAEE on hippocampal tissue from young adult and late middle-aged Wistar rats, with a focus on oxidative stress, cholinesterase activity, and neuroinflammatory markers. Methods: Ocimum americanum ethanol extract (OAEE) was incubated with hippocampal slices of young adult and late middle-aged male Wistar rats exposed to H₂O₂; an acute treatment with OAEE was evaluated in aversive memory performance and neurochemical parameters, such as hippocampal cellular oxidative state, and anticholinesterase activity, and a diet supplementation of OAEE were evaluated on several hippocampal biochemical parameters, such as oxidative state, anticholinesterase activity, and neuroinflammatory parameters in young adult and late middle-aged male rats. Results: OAEE reversed the H₂O₂-induced impaired cellular viability in hippocampal slices from young adult rats, as well as protected hippocampal slices against H₂O₂-induced damage in both young adult and late middle-aged Wistar rats, indicating its neuroprotective action. Chronic dietary OAEE supplementation reduced aging-induced increases in reactive species and lipid peroxidation levels in the hippocampus. Indeed, this supplementation reduced the TNF-α content in hippocampus from both ages, and IL-1β levels in young adult rats. Conclusions: The antioxidant actions of OAEE here observed, preventing the lipoperoxidation, as well as its anti-neuroinflammatory effect, might be related to neuroprotective effect. Our findings add evidence to support the idea of the potential use of Ocimum americanum as a nutraceutical or functional food in the aging process. Full article

Aloysia triphylla is widely used in traditional medicine from Peru for its sedative, digestive and anti-inflammatory properties. However, comprehensive studies on the biological activities of its essential oil (EO), particularly from Peruvian sources, remain limited. This study aimed to analyze the chemical composition and enantiomeric profile of A. triphylla EO and evaluate its antibacterial, antioxidant, anticholinesterase, and cytotoxic activities. The EO was obtained by steam distillation and analyzed using gas chromatography–mass spectrometry (GC-MS). A total of 62 compounds were identified, with (E)-caryophyllene (16.80%), β-pinene (9.96%), and germacrene D (10.00%) being the major components. Enantiomeric analysis revealed specific chiral signatures, including (−)-α-pinene, (+)-limonene, and (R)-(−)-linalool. The EO exhibited significant antibacterial activity, particularly against Bacillus subtilis (MIC = 5 µg/mL), and weak antioxidant activity (IC₅₀ = 7720 and 4648 µg/mL for DPPH and ABTS, respectively). Additionally, the EO demonstrated moderate acetylcholinesterase inhibition (IC₅₀ = 87.8 µg/mL) and cytotoxicity in the Artemia salina assay (LC₅₀ = 964 µg/mL). These findings suggest that A. triphylla EO possesses promising bioactivities with potential applications in pharmaceutical and cosmetic fields. Full article

An important field of research in medicinal and organic chemistry involves halogen-containing heterocyclic synthones, which form the backbone of more complex organic compounds. This study aimed to design and synthesize 28 novel derivatives of 7-aryl-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one. The derivatives were created from 7-bromoquinoline intermediates to evaluate their potential as cholinesterase inhibitors for treating neurodegenerative diseases such as Alzheimer’s disease. The conditions for the Suzuki–Miyaura cross-coupling reaction were optimized to improve yield and purity. The derivatives were evaluated for their anticholinesterase activity using Ellman’s method, revealing that it most effectively inhibited cholinesterase within the micromolar range. 7-(3-Chloro-4-fluorophenyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one derivative exhibited the highest inhibitory potency, with an IC₅₀ value of 6.084 ± 0.26 μM. Additionally, molecular dynamics simulations provided insight into how this lead compound interacts with the enzyme, suggesting its potential as a drug candidate for Alzheimer’s disease. Full article

Chemical analysis of the hydroethanolic Hypericum repens L. extracts was performed using the LC/Q-TοF/HRMS technique. The majority of compounds identified belonged to phenolics, particularly flavonoids. The extract was also studied for its possible bioactivities, demonstrating high antioxidant properties compared to the control (IC₅₀ values ranging from 4.6 to 9.42 μg/mL). Significant antibacterial activity was also detected against Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, and Salmonella enteritidis, with MIC values from 125 to 625 μg/mL. S. aureus presented the highest susceptibility among all bacteria tested. Additionally, the extract showed very mild anticholinesterase activity in the AChE and BChE inhibition assays. These findings provide the first insights into the phytochemical composition, as well as the antioxidant, antimicrobial, and anticholinesterase activities of H. repens extract, suggesting that the endemic Cyprus H. repens is a valuable natural rich source of bioactive compounds with a potentially broad range of bioactivities. Full article

In Argentina and globally, pistachio (Pistacia vera) production has significantly grown, driven by its high nutritional value and food industry demand. Its harvesting and processing generate about 40% of pistachio waste (PW), including leaves, twigs, seed coats, green, and empty kernels. Underutilized PW has led to environmental problems, including soil and water contamination by landfill accumulation. However, it could be a potential source of undiscovered bioactive compounds. This study aimed to characterize the chemical profile and to evaluate the bioactive properties of PW. The dried pistachio waste (dPW) was used to prepare the pistachio waste decoction (PWD) (10% w/v). The total phenolic content (TPC) and flavonoid content (FC) were quantified, and the chemical profile was analyzed using UPLC-DAD-ESI-MS/MS. Nematicidal activity against Meloidogyne incognita (J2), acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition, antioxidant capacity (ABTS, DPPH, FRAP), and phytotoxicity on Allium cepa, Lactuca sativa, and Raphanus sativus were evaluated. The UPLC-DAD-ESI-MS/MS analysis identified 26 compounds, including phenolics, flavonoids, and unsaturated fatty acids. The main compounds were gallic acid, anacardic acid, and quercetin derivatives. The TPC and FC were 212.65 mg GAE/g dPW and 0.022 mg QE/g dPW, respectively, displaying strong antioxidant activity across the assays DPPH, ABTS, and FRAP. PWD exhibited nematicidal activity against M. incognita (J2) (LC₅₀ = 0.12% at 24 h). Alterations in the cuticle were observed, including structural disorganization and detachment from internal tissues. Additionally, a remarkable cholinesterase inhibitory effect was detected at 2.0% PWD (42.65% for AChE and 58.90% for BuChE). PWD showed low phytotoxic effects across the tested species, and the germination percentage (GP) and the mean germination time (MGT) were not significantly affected (GP > 79%). These findings highlight the potential of PW as a sustainable alternative for M. incognita control, the remarkable nematicidal, anticholinesterase, and antioxidant properties, and the low phytotoxicity, supporting its use in sustainable agricultural practices. Full article