Search Results (328)

Parkinson’s disease (PD) is recognized as one of the most common neurodegenerative disorders globally. The primary factor contributing to this condition is the loss of dopaminergic neurons, which results in both motor and nonmotor symptoms. The etiology of neurodegeneration remains unclear. However, it is characterized by the elevated production of reactive oxygen species, which subsequently leads to oxidative stress, lipid peroxidation, mitochondrial dysfunction, and inflammation. The investigation of the applicability of natural compounds and their derivatives to various diseases is becoming increasingly important. The possible role of curcumin from Curcuma longa L. and its derivatives in the treatment of PD has been partially investigated, but there are no data on the action of synthetic cyclic C₅-curcuminoids and chalcones tested in a Parkinson’s model. Two chalcones and five synthetic cyclic C₅-curcuminoids with potential antioxidant properties were investigated in an in vitro model of 6-hydroxydopamine (6-OHDA)-induced neurodegeneration in differentiated SH-SY5Y cells. Reactive oxygen species (ROS) production, total antioxidant capacity, antioxidant enzyme activity, thiol and ATP levels, caspase-3 activity, and cytokine release were examined after treatment with the test compounds. Based on these results, one cyclic chalcone (compound 5) and three synthetic cyclic C₅-curcuminoids (compounds 9, 12, and 13) decreased oxidative stress and apoptosis in our in vitro model of neurodegeneration. Compounds 5 and 9 were also successful in decreasing the production of pro-inflammatory cytokines (IL-6, IL-8, and TNF-α), while promoting the release of anti-inflammatory cytokines (IL-4 and IL-10). These findings indicate that these two compounds exhibit potential antioxidant, anti-apoptotic, and anti-inflammatory properties, rendering them promising candidates for drug development. Full article

The pyrin domain-containing protein 3 (NLRP3) inflammasome may be a potential target for the treatment of inflammatory bowel disease (IBD), and inhibiting the activation of the NLRP3 inflammasome is of great significance for the treatment of IBD. In this study, 27 novel chalcone derivatives were designed and synthesized. Enzyme-linked immunosorbent assay (ELISA) analysis revealed that most of the compounds inhibited IL-1β secretion, with F14 exhibiting the most significant activity, showing IC₅₀ values of 0.74 μM (mouse bone marrow-derived macrophage, BMDM) and 0.88 μM (Tohoku Hospital Pediatrics-1, THP-1), respectively. Flow cytometry and immunofluorescence analysis revealed that F14 had no effect on mitochondrial reactive oxygen species (ROS) production or mitochondrial damage, nor did it affect the expression of key protein components of the NLRP3 inflammasome. Western blot and computational docking studies suggested that F14 may exert anti-inflammatory activity by targeting NLRP3 to block the oligomerization and speck formation of ASC protein. In vivo studies demonstrated that F14 exhibited significant therapeutic effects on dextran sulfate sodium (DSS)-induced acute colitis in mice. Overall, this work provides candidate compounds for the development of NLRP3 inflammasome inhibitors and the treatment of inflammatory diseases caused by NLRP3 inflammasome activation. Full article

Aizoon africanum (L.) Klak (Synonym Galenia africana L.) is traditionally used for a variety of medicinal purposes; however, it has been reported to cause liver damage and severe ascites, particularly in sheep and Angora goats in the arid regions of the Western Cape. This study explores its cytotoxic properties to identify potential cytotoxic compound(s) in the plant. The methanolic extract of A. africanum was re-investigated and subjected to various chromatographic techniques, including preparative HPLC, resulting in the isolation of eight compounds (1–8). Structural elucidation was primarily based on NMR data. Among the isolated compounds, four were flavanones, one was a flavonone, and three were chalcones. Notably, compound 8 was identified as a new chalcone, while compounds 2 and 3 were reported for the first time from this plant. The toxicity of these isolated compounds was evaluated against the HepG2 and SH-SY5Y cancer cell lines using the MTT assay. We further investigated markers of cell death using spectrophotometric and luminometric methods. Among the isolated compounds, 7 and 8 exhibited cytotoxic activities within the range of 3.0–20.0 µg/mL. Notably, the compounds demonstrated greater cytotoxicity towards liver-derived HepG2 cells compared to the neuronal SH-SY5Y cell line. Compound 7 (2′,4′-dihydroxychalcone) was identified as inducing apoptosis through the intrinsic pathway without causing overt necrosis. The findings indicate that the phytochemicals derived from A. africanum exhibit differential cytotoxic effects based on cell type, suggesting potential for developing novel anticancer agents, particularly compound 7. Additionally, the identification of compound 8 provides insight into the liver toxicity of this plant observed in sheep in South Africa. Full article

Fine particulate matter (PM_2.5) exposure has been linked to increased lung damage due to compromised vascular barrier function, while 3-deoxysappanchalcone (3-DSC), a chalcone derived from Caesalpinia sappan, is known for its pharmacological benefits such as anti-cancer, anti-inflammatory, and antioxidant effects; however, its potential role in mitigating PM_2.5-induced pulmonary damage remains unexplored. To confirm the inhibitory effects of 3-DSC on PM_2.5-induced pulmonary injury, this research focused on evaluating how 3-DSC influences PM_2.5-induced disruption of the barrier of the endothelial cells (ECs) in the lungs and the resulting pulmonary inflammation. Permeability, leukocyte migration, proinflammatory protein activation, reactive oxygen species (ROS) generation, and histology were assessed in PM_2.5-treated ECs and mice. This study demonstrated that 3-DSC effectively neutralized the reactive oxygen species (ROS) generated by PM_2.5 exposure in the lung endothelial cells, suppressing ROS-triggered p38 MAPK activation while enhancing Akt signaling pathways critical to preserving vascular barrier function. In animal models, 3-DSC administration markedly decreased vascular permeability, attenuated the influx of immune cells into the lung tissue, and lowered inflammatory mediators like cytokines in the airways of PM_2.5-exposed mice. These data suggest that 3-DSC might exert protective effects on PM_2.5-induced inflammatory lung injury and vascular hyperpermeability. Full article

This study details how 3-(naphthalen-2-yl)-1-phenylprop-2-en-1-one (3NPEO) behaves in terms of photophysics when exposed to different solvents. The solvatochromic effect study reveals significant polarity shifts in the excited states of the 3NPEO compound, likely due to an intramolecular proton transfer mechanism. Measurements of dipole moments provide insight into their resonance structures in both ground and excited states. Electrochemical analysis revealed a reversible redox process, indicating a favorable charge transport potential. HOMO and LUMO energies of the compound were computed via oxidation and reduction potential standards. 3NPEO exhibits optimal one-photon and two-photon absorption characteristics, validating its suitability for visible wavelength laser applications in photonic devices. Furthermore, molecular docking and dynamics simulations demonstrated strong interactions between 3NPEO and the progesterone receptor enzyme, supported by structure–activity relationship (SAR) analyses. In vitro cytotoxicity assays on the MDAMB-231 breast cancer cell line showed moderate tumor cell inhibitory activity. Apoptosis studies confirmed the induction of both early and late apoptosis. These findings suggest that 3NPEO holds promise as a potential anticancer agent targeting the progesterone receptor in breast cancer cells. Overall, the findings highlight the substantial influence of solvent polarity on the photophysical properties and the design of more effective and stable therapeutic agents. Full article

Estrogen receptor alpha (ERα) plays a vital role in the development and progression of breast cancer by regulating the expression of genes associated with cell proliferation in breast tissue. ERα inhibition is a key strategy in the prevention and treatment of breast cancer. Previous research modified chalcone compounds into pyrazoline benzenesulfonamide derivatives (Modifina) which show activity as an ERα inhibitor. This study aimed to design novel pyrazoline benzenesulfonamide derivatives (PBDs) as ERα antagonists using in silico approaches. Structure-based and ligand-based drug design approaches were used to create drug target molecules. A total of forty-five target molecules were initially designed and screened for drug likeness (Lipinski’s rule of five), cytotoxicity, pharmacokinetics and toxicity using a web-based prediction tools. Promising candidates were subjected to molecular docking using AutoDock 4.2.6 to evaluate their binding interaction with ERα, followed by molecular dynamics simulations using AMBER20 to assess complex stability. A pharmacophore model was also generated using LigandScout 4.4.3 Advanced. The molecular docking results identified PBD-17 and PBD-20 as the most promising compounds, with binding free energies (ΔG) of −11.21 kcal/mol and −11.15 kcal/mol, respectively. Both formed hydrogen bonds with key ERα residues ARG394, GLU353, and LEU387. MM-PBSA further supported these findings, with binding energies of −58.23 kJ/mol for PDB-17 and −139.46 kJ/mol for PDB-20, compared to −145.31 kJ/mol, for the reference compound, 4-OHT. Although slightly less favorable than 4-OHT, PBD-20 demonstrated a more stable interaction with ERα than PBD-17. Furthermore, pharmacophore screening showed that both PBD-17 and PBD-20 aligned well with the generated model, each achieving a match score of 45.20. These findings suggest that PBD-17 and PBD-20 are promising lead compounds for the development of a potent ERα inhibitor in breast cancer therapy. Full article

Human coronaviruses are a group of viruses that continue to threaten human health. In this study, we investigated the antiviral activity of 4-hydroxychalcone (4HCH), a chalcone derivative, against human coronavirus HCoV-OC43. We found that 4HCH significantly inhibited the cytopathic effect, reduced viral protein and RNA levels in infected cells, and increased the survival rate of HCoV-OC43-infected suckling mice. Mechanistically, 4HCH targets the early stages of viral infection by binding to the epidermal growth factor receptor (EGFR) and inhibiting the EGFR/AKT/ERK1/2 signaling pathway, thereby suppressing viral replication. Additionally, 4HCH significantly reduced the production of pro-inflammatory cytokines and chemokines in both HCoV-OC43-infected RD cells and a suckling mouse model. Our findings demonstrate that 4HCH exhibits potent antiviral activity both in vitro and in vivo, suggesting its potential as a therapeutic agent against human coronaviruses. This study highlights EGFR as a promising host target for antiviral drug development and positions 4HCH as a candidate for further investigation in the treatment of coronavirus infections. Full article

Chemical products, including cleaning agents, disinfectants, stain removers, and cosmetics, release harmful chemicals that pose a risk to human health and the environment, necessitating alternative sources. The objective of this research was to identify the most effective phytoextract from food production waste for use in sustainable aerosol hygiene technology as an electrostatic bio-disinfectant. The investigation was performed through wipe tests and airborne microbial collection techniques. The upgraded coffee silverskin phytoextract demonstrated superior disinfection potential for various surfaces and airborne microbes compared to the hot trub phytoextract, with an industrial disinfectant serving as the control. Log reduction analyses revealed a more significant killing efficacy (p ≤ 0.05, using the ANOVA test) against Gram-positive organisms (Bacillus subtilis and Listeria monocytogenes) than against Gram-negative organisms (Escherichia coli and Vibrio parahaemolyticus), with the log reductions ranging from 3.08 to 5.56 and 3.72 to 5.81, respectively. Chemical characterization by LC-ESI-QTOF-MS, ¹H NMR, and FTIR showed that CGAs and chalcones are the most bioactive compounds in CSS and HT, respectively. The innovation in this work involves an integrated approach that combines waste-derived phytoextracts, advanced chemical profiling, and scalable aerosol disinfection. Furthermore, this research offers a greener, cost-effective, and industrially relevant alternative to synthetic chemical disinfectants. The interdisciplinary approach contributes to the development of bio-based disinfectants for use in the food industry, hospitals, and public health settings. This investigation supports a paradigm shift toward sustainable disinfection practices, thereby improving food and environmental safety. Full article

Skin aging is mainly caused by external factors like sunlight, which triggers oxidative stress and chronic inflammation. Natural halogenated flavonoids have demonstrated anti-inflammatory properties. Inspired by the macroalgae-derived bromophenol BDDE, we investigated the anti-inflammatory potential of structure-related chalcones (1–7). Chalcones 1 and 7 showed the least cytotoxicity in keratinocyte and macrophage cells. Chalcones 1, 2, 4, and 5 exhibited the most significant anti-inflammatory effects in murine macrophages after lipopolysaccharide stimulation, with chalcone 1 having the lowest IC₅₀ value (≈0.58 μM). A SNAP assay confirmed that chalcones do not exert their effects through direct NO scavenging. Symmetrical bromine atoms and 3,4-dimethoxy groups on both aromatic rings improved the anti-inflammatory activity, indicating a relevant structure–activity relationship. Chalcones 1 and 2 were selected for study to clarify their mechanisms of action. At a concentration of 7.5 μM, chalcone 2 demonstrated a rapid and effective inhibitory action on the protein levels of inducible nitric oxide synthase (iNOS), while chalcone 1 exhibited a gradual inhibitory action. Moreover, chalcone 1 effectively activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway with around a 3.5-fold increase at the end of 24 h at 7.5 μM, highlighting its potential as a modulator of oxidative stress responses. These findings place chalcone 1 as a promising candidate for skincare products targeting inflammation and skin aging. Full article

The excessive use of synthetic pesticides has not only resulted in increased resistance among weeds and pests, leading to significant economic loss, but has also raised serious health and environmental concerns. Chalcones and their derivatives, known for their herbicidal, fungicidal, bactericidal, and antiviral properties, are emerging as promising bio-based candidates. These naturally occurring compounds have long been recognized for their beneficial health effects and wide-range applications. However, their limited concentration in plants, along with poor solubility and bioavailability, brings challenges for their development. The aim of this study was to examine the properties of a synthetic substance, pinocembrin dihydrochalcone (3-phenyl-1-(2,4,6-trihydroxyphenyl)-1-propanone), including its soil dissipation and adsorption. Additionally, we evaluated its antioxidant activity through the DPPH assay and FRAP experiments. This analysis aims to provide insights into its potential classification as a low risk pesticide. Full article

Twenty-one novel chalcone derivatives, 5a-5u, incorporating a diphenyl ether moiety, were designed, prepared, and subsequently characterized using NMR and HR-MS and FR-IR techniques. Antibacterial evaluation of the target compounds was carried out against Staphylococcus aureus, Escherichia coli, Salmonella, and Pseudomonas aeruginosa. The in vitro results demonstrated that most compounds exhibited considerable potency in inhibiting bacterial growth, with MIC values ranging from 25.23 to 83.50 μM for S. aureus, 27.53 to 76.25 μM for E. coli, 29.73 to 71.73 μM for Salmonella, and 27.53 to 71.73 μM for P. aeruginosa. Notably, all synthesized compounds exhibited superior antibacterial activity compared to the lead chalcone. In particular, compound 5u, which features two diphenyl ether moieties, displayed outstanding antibacterial performance, with MIC values of 25.23 μM for S. aureus and 33.63 μM for E. coli, Salmonella, and P. aeruginosa. Moreover, compound 5u outperformed both ciprofloxacin and gentamicin against Salmonella and P. aeruginosa, and time-kill curve assays further revealed that concentrations of compound 5u at or above 33.63 μM provided potent and sustained inhibition of both Salmonella and P. aeruginosa. Additionally, molecular modeling of the P. aeruginosa LpxC-compound 5u complex suggested that compound 5u could strongly bind to and interact with the binding site of the LpxC. Based on these findings, compound 5u represents a promising lead for future antimicrobial development. Full article

Prenylated chalcones have garnered attention as potential anticancer agents due to their ability to modulate multiple cancer-related pathways. In this study, we synthesized and evaluated nine novel prenylated chalcone derivatives for their antiproliferative effects against castration-resistant prostate cancer (CRPC) cell lines, DU145 and PC3. Among these, compounds 6d and 7j demonstrated potent cytotoxic activity, with IC₅₀ values comparable to cisplatin, and exhibited selective toxicity towards cancer cells over non-tumorigenic RWPE-1 cells. Mechanistic investigations revealed that these compounds induce apoptosis via mitochondrial membrane depolarization and increased late apoptotic events. Flow cytometry confirmed activation of both early and late apoptotic pathways. These findings highlight the potential of chalcone derivatives 6d and 7j as promising therapeutic candidates for CRPC treatment and support further development of chalcone-based molecules in precision oncology. Full article

Flavonoids and chalcones, widely recognised for their diverse biological activities, have garnered attention due to their potential therapeutic applications. This review discusses fluorinated flavonoids and chalcones, focusing on their prospective anti-inflammatory, antidiabetic, anticancer, antiosteoporotic, cardioprotective, neuroprotective, hepatoprotective, antimicrobial, and antiparasitic applications. The enhanced biological activities of fluorinated derivatives, particularly the antibacterial, antiviral, and anticancer properties, are attributed to the introduction of fluorine groups, which increase lipophilicity and metabolic stability. Key findings indicate that fluorinated flavonoids and chalcones exhibit synergistic effects with antibiotics, inhibit bacterial efflux pumps, and reveal potent antiviral and anticancer properties. However, challenges such as cytotoxicity and structural optimisation have to be addressed. The synthesis of fluorinated flavonoids and chalcones is discussed, with emphasis on various synthetic methods such as condensation and cyclisation reactions starting from fluorinated precursors, as well as fluorination strategies, including the use of molecular fluorine or fluorinating agents. Fluorinated flavonoids and chalcones represent candidates for therapeutic development and have the potential to overcome drug resistance. However, further studies are necessary to adjust their pharmacological profiles. Full article

Chrysanthemum indicum L. is characterized by a high concentration of flavonoid compounds, which exert multifaceted influences on the organoleptic properties, chromatic stability, and therapeutic efficacy of capitulum-derived extracts. These components exhibit diverse biological activities, including heat-clearing, antibacterial, and hepatoprotective properties. A novel white C. indicum variant lacking linarin was recently identified, but its metabolic and transcriptional differences from traditional yellow varieties remain unclear. This study compared flavonoid metabolism in white mutant (BHYJ) and yellow (HJ06) varieties through integrated metabolomic and transcriptomic analyses. Metabolomics identified 491 flavonoids, revealing distinct accumulation patterns: BHYJ accumulated dihydroflavones/chalcones (eriodictyol, hesperetin-8-C-glucoside-3′-O-glucoside, naringenin chalcone), while HJ06 showed higher flavones/flavonols (linarin, rhoiflolin, vitexin, rutin, nicotiflorin). Transcriptomics identified 43 differentially expressed enzyme genes, with key regulators FNSII, F3′H, and F3H showing expression patterns correlating with metabolite profiles. Integrated analysis revealed metabolic divergence at the naringenin node: BHYJ produced less naringenin than HJ06 and preferentially channeled it toward eriodictyol synthesis rather than linarin production. This metabolic shift explains the reduced linarin accumulation in BHYJ. Experimental validation confirmed the coordinated expression patterns of key enzymes. These findings provide foundational insights into transcriptional regulation of flavonoid divergence in pigmented C. indicum varieties, establishing a framework for elucidating enzymatic control of flavonoid biosynthesis in capitulum development. Full article

Butein (3,4,2′,4′-tetrahydroxycalone) is a chalcone derivative and plant polyphenol extracted from Rhus verniciflua Stokes. Butein has an open C-ring structure and a variety of biological activities. Molecular mechanisms by which butein could affect cell viability, ROS levels, mitochondrial function, apoptosis, and necrosis in prostate cancer cells were investigated using 2D monolayer and 3D sphere culture systems. Cytotoxicity and cell cycle monitoring showed that butein treatment decreased cell viability and increased peaks of sub-G₀/G₁ and G₂/M phases analyzed by flow cytometry. These changes were observed with a concurrent induction of DNA damage, apoptosis, and necrosis. Although 3D spheres treated with butein showed decreased cell viability, they were slightly more resistant than cells in 2D cultures. This phenomenon was accompanied by an increase in mediators of apoptosis and necrosis. Monitoring changes of apoptosis-related proteins via Western blot showed that butein decreased caspase-3, PARP, and Bcl-2, but increased Bax. Meanwhile, butein increased levels of p-receptor interacting serine/threonine–protein kinase 3 (p-RIP3) and p-mixed lineage kinase domain-like kinase (p-MLKL) known to be mediators of necrosis. Overall, our data suggest that butein can induce apoptosis and necrosis of prostate cancer cells by regulating pro- and anti-apoptotic proteins via ROS. Thus, butein might be a potential agent for treating prostate cancer. Full article