Search Results (3,630)

The high incidence of melanoma leading to a poor prognosis rate endorses the development of alternative and innovative approaches in the treatment of melanoma. Therefore, the present study aims to develop and characterize, in terms of physicochemical features and biological impact, an aqueous suspension of magnetite (Fe₃O₄) coated with β-cyclodextrin (Fe₃O₄@β-CD) as a potential innovative alternative nanosystem for melanoma therapy. The nanosystem exhibited physicochemical characteristics suitable for biological applications, revealing a successful complexation of Fe₃O₄ NPs with β-CD and an average size of 18.1 ± 2.1 nm. In addition, the in vitro evaluations revealed that the newly developed nanosystem presented high biocompatibility on a human keratinocyte (HaCaT) monolayer and selective antiproliferative activity on amelanotic human melanoma (A375) cells, inducing early apoptosis features when concentrations of 10, 15, and 20 μg/mL were employed for 48 h and 72 h. Collectively, the Fe₃O₄@β-CD nanosystem reveals promising features for an adjuvant approach in melanoma treatment, mainly due to its β-cyclodextrin coating, thus endorsing a potential co-loading of therapeutic drugs. Furthermore, the intrinsic magnetic core of Fe₃O₄ NPs supports the magnetically based cancer treatment strategies. Full article

Cancer is one of the most lethal diseases of this century. Unfortunately, many anticancer agents have harsh side effects or fail to work against cancer any longer due to tolerance. Dihydropyrimidinones are promising structures containing a pyrimidine ring. Targeting Eg5 is their most well-known activity. Inhibition of this enzyme gives them the privilege of strong cytotoxic activity with less side effects. Phenyl ring is a group that can be found in the majority of organic molecules and possesses preferable pharmacokinetic and pharmacodynamic characteristics. This review studies DHPM derivatives that are substituted with a phenyl ring and possess antiproliferative ability by inhibiting Eg5. The compounds are able to inhibit different cancer cell lines, and some are more potent than the standard drug. The biological results are in accordance with the docking studies. Full article

Background/Objectives: Cancer suffers from unresolved therapeutic challenges owing to the lack of targeted therapies and heightened recurrence risk. This study aimed to investigate the new series of hydroxamate by structurally modifying the pharmacophore of vorinostat. Methods: The present work involves the synthesis of 15 differently substituted 2H-1,2,3-triazole-based hydroxamide analogs by employing triazole ring as a cap with varied linker fragments. The compounds were evaluated for their anticancer effect, especially their anti-breast cancer response. Molecular docking and molecular dynamics simulations were conducted to examine binding interactions. Results: Results indicated that among all synthesized hybrids, the molecule VI(i) inhibits the growth of MCF-7 and A-549 cells (GI₅₀ < 10 μg/mL) in an antiproliferative assay. Compound VI(i) was also tested for cytotoxic activity by employing an MTT assay against A549, MCF-7, and MDA-MB-231 cell lines, and the findings indicate its potent anticancer response, especially against MCF-7 cells with IC₅₀ of 60 µg/mL. However, it experiences minimal toxicity towards the normal cell line (HEK-293). Mechanistic studies revealed a dual-pathway activation: first, apoptosis (17.18% of early and 10.22% of late apoptotic cells by annexin V/PI analysis); second, cell cycle arrest at the S and G2/M phases. It also promotes ROS generation in a concentration-dependent manner. The HDAC–inhibitory assay, extended in silico molecular docking, and MD simulation experiments further validated its significant binding affinity towards HDAC 1 and 6 isoforms. DFT and ADMET screening further support the biological proclivity of the title compounds. The notable biological contribution of VI(i) highlights it as a potential candidate, especially against breast cancer cells. Full article

Noncommunicable diseases (NCDs) like diabetes and cancer drive demand for therapeutic functional foods. This study developed freeze-dried fermented camel milk (FCM) with Ajwa date pulp (ADP), evaluating its physical and functional properties, probiotic survival, and potential benefits for diabetes and cancer. To achieve this target, six FCM formulations were prepared using ABT-5 starter culture (containing Lactobacillus acidophilus, Bifidobacterium bifidum, and Streptococcus thermophilus) with or without Lacticaseibacillus rhamnosus B-1937 and ADP (12% or 15%). The samples were freeze-dried, and their functional properties, such as water activity, dispersibility, water absorption capacity, water absorption index, water solubility index, insolubility index, and sedimentation, were assessed. Reconstitution properties such as density, flowability, air content, porosity, loose bulk density, packed bulk density, particle density, carrier index, Hausner ratio, porosity, and density were examined. In addition, color and probiotic survivability under simulated gastrointestinal conditions were analyzed. Also, antidiabetic potential was assessed via α-amylase and α-glucosidase inhibition assays, while cytotoxicity was evaluated using the MTT assay on Caco-2 cells. The results show that ADP supplementation significantly improved dispersibility (up to 72.73% in FCM15D+L). These improvements are attributed to changes in particle size distribution and increased carbohydrate and mineral content, which facilitate powder rehydration and reduce clumping. All FCM variants demonstrated low water activity (0.196–0.226), indicating good potential for shelf stability. The reconstitution properties revealed that FCM powders with ADP had higher bulk and packed densities but lower particle density and porosity than controls. Including ADP reduced interstitial air and increased occluded air within the powders, which may minimize oxidation risks and improve packaging efficiency. ADP incorporation resulted in a significant decrease in lightness (L*) and increases in redness (a*) and yellowness (b*), with greater pigment and phenolic content at higher ADP levels. These changes reflect the natural colorants and browning reactions associated with ADP, leading to a more intense and visually distinct product. Probiotic survivability was higher in ADP-fortified samples, with L. acidophilus and B. bifidum showing resilience in intestinal conditions. The FCM15D+L formulation exhibited potent antidiabetic effects, with IC₅₀ values of 111.43 μg mL⁻¹ for α-amylase and 77.21 μg mL⁻¹ for α-glucosidase activities, though lower than control FCM (8.37 and 10.74 μg mL⁻¹, respectively). Cytotoxicity against Caco-2 cells was most potent in non-ADP samples (IC₅₀: 82.22 μg mL⁻¹ for FCM), suggesting ADP and L. rhamnosus may reduce antiproliferative effects due to proteolytic activity. In conclusion, the study demonstrates that ADP-enriched FCM is a promising functional food with enhanced probiotic viability, antidiabetic potential, and desirable physical properties. This work highlights the potential of camel milk and date synergies in combating some NCDs in vitro, suggesting potential for functional food application. Full article

Background/Objectives: Humulus lupulus (hops) are a perennial, dioecious plant widely cultivated for beer production, used for their distinguishing aroma and bitterness—traits that confer high added value status. Various hop-derived compounds have been reported to exhibit antioxidant, antimicrobial, antiproliferative and other bioactive effects. This systematic review and meta-analysis assesses the impact of hop compounds on the viability of diverse cancer cell lines. Methods: A comprehensive literature search was performed following PRISMA guidelines. Data were synthesized via multivariate meta-analysis and meta-regression, using IC₅₀ values as the effect size. Key variables included assay type (SRB, tetrazolium salt-based, crystal violet), exposure duration (24, 48, 72 h), specific hop compound and cancer cell line. Results: Of 622 articles identified, 61 met eligibility criteria, yielding 354 individual experiments. Meta-regression of xanthohumol (XN) IC₅₀ values across SRB, tetrazolium and crystal violet assays revealed no statistically significant differences at 24 h (p = 0.77), 48 h (p = 0.35) and 72 h (p = 0.70), supporting the interchangeability of the methods. Meta-analysis confirmed that hop constituents inhibit cancer cell proliferation; XN emerged as the most potent flavonoid (IC₅₀ = 16.89 μM at 72 h), while lupulone was the strongest compound overall (IC₅₀ = 5.00 μM at 72 h). Crude hop extracts demonstrated greater antiproliferative selectivity for cancer versus non-cancer cells (IC₅₀ = 35.23 vs. 43.80 μg/mL at 72 h). Conclusions: Hop compounds, and particularly bitter acids, demonstrate promising antiproliferative activity against cancer cells with comparatively low toxicity to healthy cells. Furthermore, our analysis confirms the comparability of SRB, tetrazolium-based and crystal violet assays, supporting the robust integration of antiproliferative data. Full article

Apples and Korean green chili peppers are rich in phytochemicals and recognized for their diverse bioactive properties. Given the potential to enhance these beneficial compounds, this study investigated the effects of mineral supplementation during cultivation on the antioxidant and antiproliferative activities of extracts from both crops. Mineral-enriched cultivation significantly increased the total phenolic and flavonoid contents in both crops, which was accompanied by enhanced DPPH and ABTS radical scavenging activities. Moreover, the mineral-supplemented extracts of Korean green chili pepper activated the Nrf2 signaling pathway and upregulated downstream antioxidant enzymes, including heme oxygenase-1 (HO-1), γ-glutamylcysteine ligase (GCL), and glutathione peroxidase (GPx). Notably, the mineral-supplemented Korean green chili pepper extract significantly suppressed the proliferation of human colorectal cancer cells. These findings suggest that mineral supplementation during cultivation may improve the functional quality of apples and Korean green chili peppers, supporting their potential application in cancer prevention and complementary therapeutic strategies. Full article

Lymphoma continues to pose a serious challenge to global health, underscoring the urgent need for new therapeutic strategies. Recently, the gut microbiome has been shown to play a potential role in regulating immune responses and influencing cancer progression. However, its molecular mechanisms of action in lymphoma remain poorly understood. This study investigates the antiproliferative and apoptotic activities of gut microbiota-derived metabolites, specifically nisin (N) and urolithin B (UB), individually and in combination 7:3 (5750 μM), against the human lymphoma cell line HKB-11. Comprehensive evaluations were performed using Alamar Blue viability assays, combination index (CI) analyses, reactive oxygen species (ROS) quantification, flow cytometry for apoptosis detection, and advanced bottom-up proteomics analyses. N and UB exhibited potent antiproliferative activity, with the 7:3 combination demonstrating strong synergistic effects (CI < 1), significantly enhancing apoptosis (p < 0.01) and ROS production (p < 0.0001) compared to the untreated control. Proteomics analyses revealed substantial alterations in proteins crucial to ribosomal biogenesis, mitochondrial function, cell cycle control, and apoptosis regulation, including a marked downregulation of ribosomal proteins (RPS27; Log₂FC = −3.47) and UBE2N (Log₂FC = −0.60). These findings highlight the potential of N and UB combinations as a novel and practical therapeutic approach for lymphoma treatment, warranting further in vivo exploration and clinical validation. Full article

Background: Short-chain fatty acids (SCFAs), microbial metabolites also known as postbiotics, are essential for maintaining gut health. However, their antiproliferative effects on gastric cancer cells and potential interactions with conventional therapies remain underexplored. This study aimed to investigate the effects of three SCFA salts—magnesium acetate (A), sodium propionate (P), and sodium butyrate (B)—individually and in combination (APB), as well as in combination with dexamethasone (Dex), on AGS gastric adenocarcinoma cells. Methods: AGS cells were treated with PB, AP, AB, APB, Dex, and APB+Dex. Cell viability was assessed to determine antiproliferative effects, and the IC₅₀ of APB was calculated. Flow cytometry was used to evaluate apoptosis and necrosis. Reactive oxygen species (ROS) levels were measured to assess oxidative stress. Proteomic analysis via LC-MS was performed to identify differential protein expression and related pathways impacted by the treatments. Results: SCFA salts showed significant antiproliferative effects on AGS cells, with APB exhibiting a combined IC₅₀ of 568.33 μg/mL. The APB+Dex combination demonstrated strong synergy (combination index = 0.76) and significantly enhanced growth inhibition. Both APB and APB+Dex induced substantial apoptosis (p < 0.0001) with minimal necrosis. APB alone significantly increased ROS levels (p < 0.0001), while Dex moderated this effect in the combination group APB+Dex (p < 0.0001). Notably, the APB+Dex treatment synergistically targeted multiple tumour-promoting mechanisms, including the impairment of redox homeostasis through SLC7A11 suppression, and inhibition of the haemostasis, platelet activation network and NF-κB signalling pathway via downregulation of NFKB1 (−1.34), exemplified by increased expression of SERPINE1 (1.99) within the “Response to elevated platelet cytosolic Ca²⁺” pathway. Conclusions: These findings showed a multifaceted anticancer mechanism by APB+Dex that may collectively impair cell proliferation, survival signalling, immune modulation, and tumour microenvironment support in gastric cancer. Full article

The synthesis of 2-phenylbenzoxazole fluorosulfate derivatives was carried out using the SuFEx reaction. To study the anticancer properties of the obtained compounds, the cell lines PC-3 (obtained from prostate adenocarcinoma), BT-474, and MCF-7 (both obtained from breast carcinoma) were used. The cytotoxicity on murine 3T3L1 embryonic was also investigated. Among the tested compounds, the ortho-substituted fluorosulfate derivative (BOSo) exhibited significant cytotoxicity against MCF-7 cells. The biological findings are consistent with molecular docking results, which revealed a structural similarity between BOSo and known inhibitors of hER and HER2 receptors—tamoxifen and SYR127063. Therefore, BOSo shows promise as a potential therapeutic agent with antiproliferative properties. The photoluminescent characteristics of the fluorosulfate derivatives were examined in the solid state, in acetonitrile solution and in PBS, with the highest quantum yields reaching up to 64% for the para-fluorosulfate derivative in acetonitrile. Overall, these compounds demonstrate considerable potential for the development of new multifunctional molecular tools that combine biological activity with fluorescent properties. Full article

Ferrocene (Fc), a redox-active organometallic scaffold, has attracted significant attention in medicinal chemistry due to its favorable physicochemical and pharmacological properties. The present study explores the therapeutic potential of novel Fc-functionalized analogues of imatinib and nilotinib, aimed at targeting BCR-ABL1+ chronic myeloid leukemia (CML) cells. A series of Fc-based derivatives (compounds 6, 9, 14, and 18) were synthesized by systematically substituting key pharmacophoric regions of the parent tyrosine kinase inhibitors with Fc units. The antiproliferative activity of these compounds was evaluated against four BCR-ABL1-positive leukemia cell lines (K-562, BV-173, AR-230, and LAMA-84), with imatinib serving as a reference drug. Biological assays revealed distinct structure–activity relationships. Compounds 6 and 9 demonstrated superior activity against the K-562 cell line, while compounds 14 and 18 exhibited enhanced potency and higher ligand efficiencies (LEs) against BV-173 and AR-230 cells compared to imatinib. Selectivity assays further indicated favorable toxicity profiles of compounds 9 and 14 toward malignant versus non-malignant cells. Molecular docking studies supported these findings, showing that Fc substitution alters binding interactions within the c-Abl kinase ATP-binding site while retaining key stabilizing contacts. Computationally predicted LEs showed strong correlation with experimental data, especially for K-562 and LAMA-84 cells, confirming the kinase as a relevant target. Full article

Plants of the Annona genus have garnered increasing scientific interest due to their rich phytochemical profile and broad spectrum of biological activities, which include antimicrobial, antiproliferative, and cytotoxic effects. Among the most studied compounds are acetogenins and Annonacins, which exhibit potent bioactivity and have been identified as key agents in the green synthesis and stabilization of nanomaterials. In recent years, the integration of Annona plant extracts—particularly from leaves—into nanotechnology platforms has opened new avenues in the development of eco-friendly and biocompatible nanostructures for biomedical applications. This review provides a comprehensive overview of the current knowledge regarding the antimicrobial properties of nanomaterials synthesized using extracts from Annona species. This review encompasses 74 indexed articles published between 2012 and 2023, focusing on the synthesis of nanomaterials using extracts from this genus that exhibit antimicrobial and biomedical properties. The search was conducted in databases such as Google Scholar, Web of Science, and Scopus. Emphasis is placed on their antibacterial, antifungal, and anthelmintic effects, as well as additional therapeutic potentials, such as antidiabetic, antihypertensive, antiproliferative, and cytotoxic activities. The analysis of the recent literature highlights how Annona-derived phytochemicals contribute significantly to the functionalization and enhanced biological performance of these nanomaterials. This work aims to support future research focused on the rational design of Annona-based nanostructures as promising candidates in antimicrobial and therapeutic strategies. Full article

Prostate cancer is a serious, life-threatening condition among men, usually requiring long-term chemotherapy. Due to its high efficacy, bicalutamide, a non-steroidal anti-androgen, has widespread use. However, its poor water solubility, low oral bioavailability, and nonspecific systemic exposure limit its application. To overcome these obstacles, our study explored the potential of non-carboxylated and carboxylated mesoporous carbon nanoparticles (MCN) as advanced drug carriers for bicalutamide (MCN/B and MCN-COOH/B). The physicochemical properties and release behaviour were thoroughly characterized. Functionalization with carboxylic groups significantly improved wettability, dispersion stability, as well as loading efficiency due to enhanced hydrogen bonding and π–π stacking interactions. Moreover, all systems exhibited sustained and near-infrared (NIR) triggered drug release with reduced burst-effect, compared to the release of free bicalutamide. Higher particle size and stronger drug–carrier interactions determined a zero-order kinetics and notably slower release rate of MCN-COOH/B compared to non-functionalized MCN. Cytotoxicity assays on LNCaP prostate cancer cells demonstrated that both MCN/B and MCN-COOH/B possessed comparable antiproliferative activity as free bicalutamide, where MCN-COOH/B exhibited superior efficacy, especially under NIR exposure. These findings suggest that MCN-COOH nanoparticles could be considered as a prospective platform for controlled, NIR-accelerated delivery of bicalutamide in prostate cancer treatment. Full article

Marine algae offer environmentally friendly platforms for green nanoparticle synthesis. This study reports the biosynthesis of silver nanoparticles using polysaccharides isolated from the brown alga Chnoospora minima (PAgNPs) and evaluates their therapeutic potential. Fourier Transform Infrared Spectroscopy (FTIR) confirmed algal polysaccharide functional groups. Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), and Energy Dispersive X-ray (EDX) analysis characterized the nanoparticles as spherical (~84 nm average size), stable (zeta potential −18.5 mV), and containing elemental silver without nitrogen. The PAgNPs exhibited potent antioxidant activity (~100% DPPH scavenging) and significant antimicrobial efficacy, particularly against Staphylococcus aureus and Candida species. Crucially, PAgNPs displayed potent antiproliferative activity against human lung cancer cells (A549, IC₅₀: 13.59 µg/mL). In contrast, toxicity to normal Vero cells was significantly lower (IC₅₀: 300.2 µg/mL), demonstrating notable cancer cell selectivity (SI 22.1). Moderate activity was observed against MCF-7 breast cancer cells (IC₅₀: 100.7 µg/mL). These results demonstrate that C. minima polysaccharide facilitates the synthesis of biocompatible AgNPs with promising antimicrobial and selective anticancer capabilities, highlighting their potential for further development as nanotherapeutics. Full article

The eight new copper(II), nickel(II), zinc(II), and iron(III) coordination compounds [Cu(L)Cl]₂ (1), [Cu(L)Br]₂ (2), [Cu(L)(NO₃)]₂ (3), [Cu(phen)(L)]NO₃ (4), [Ni(HL)₂](NO₃)₂·H₂O (5), [Ni(HL)₂]Cl₂ (6), [Zn(L)₂]·0.125H₂O (7), and [Fe(L)₂]Cl (8), where HL stands for 2-benzoylpyridine 4-allylthiosemicarbazone, were synthesized and characterized. ¹H, ¹³C NMR, and FTIR spectroscopies were used for characterization of the HL thiosemicarbazone. The elemental analysis, the FTIR spectroscopy, and the study of molar electrical conductivity were used for characterization of the coordination compounds 1–8. Also, the crystal structures of HL, its salts ([H₂L]Cl; [H₂L]NO₃), and complexes 1, 3, 5, 7, and 8 were determined using single-crystal X-ray diffraction analysis. Complexes 5, 7, 8 have mononuclear structures, while copper(II) complexes 1 and 3 have a dimeric structure with the sulfur atoms of the thiosemicarbazone ligand bridging two copper atoms together. Thiosemicarbazone HL and the complexes manifest antibacterial and antifungal activities. The studied substances are more active towards Gram-negative bacteria than towards Gram-positive bacteria and fungi. Complex 1 is the most active one towards Gram-positive bacteria and C. albicans, while the introduction of 1,10-phenanthroline into the inner sphere enhances the activity towards Gram-negative bacteria. Thiosemicarbazone and complexes 6 and 7 manifest antiradical activity that exceeds the activity of Trolox. HL and complex 1 manifest antiproliferative activity towards HL-60 cancer cells which exceeds the activity of their analogs with 2-formyl-/2-acetylpyridine 4-allylthiosemicarbazone. Full article

S-nitrosoglutathione (GSNO), a promising S-nitrosothiol, has been recognized for its ability to modulate vascular tone through its vasodilatory, antiplatelet, and antiproliferative effects. However, data on its vasodilatory effects in human vessels remain limited, and its mechanisms of action have yet to be fully elucidated. In this study, we aimed to investigate the vasorelaxant effect of GSNO and its underlying mechanisms, with particular focus on the soluble guanylate cyclase (sGC)/nitric oxide (NO) pathway and potassium channels in isolated human saphenous veins (SVs) obtained from patients undergoing coronary artery bypass grafting (CABG). GSNO (10⁻⁸–10⁻⁴ M) produced concentration-dependent relaxations in SV rings precontracted with phenylephrine. These relaxations were unaffected by NO synthase inhibition with L-NAME (10⁻⁴ M, 30 min) or NO scavenging with PTIO (10⁻⁴ M, 30 min), but were significantly reduced by the sGC inhibitor, ODQ (10⁻⁵ M, 30 min). Inhibition of ATP-sensitive (glibenclamid; 10⁻⁵ M, 30 min.), high-conductance Ca²⁺-activated (charybdotoxin; 10⁻⁷ M, 30 min), small-conductance Ca²⁺-activated (apamin; 10⁻⁶ M, 30 min), or voltage-dependent (4-aminopyridine; 10⁻³ M, 30 min) potassium channels did not alter the maximum relaxant responses to GSNO. Furthermore, pretreatment with GSNO (10⁻⁴ M, 30 min) significantly attenuated both the contractile response and sensitivity to phenylephrine. Collectively, these findings demonstrate that GSNO exerts acute vasorelaxant and modulatory effects in human SV primarily via cGMP-dependent mechanisms, highlighting its potential as a local therapeutic agent for preventing graft spasm in CABG. Full article