Search Results (44)

Voltage-gated potassium channel Kv1.3 plays an important role in the regulation of survival and apoptosis in many cell types, including both normal and cancer cells. Inhibitors of these channels may potentially find clinical applications in the treatment of various diseases, including certain cancers characterized by the over-expression of Kv1.3. In this study, the effects of isobavachalcone (IBC) and two non-prenylated chalcones—2′-hydroxy-4,3′-dimethoxychalcone (HDC) and 2′-hydroxy-2-methoxychalcone (HMC)—on Kv1.3 channel activity were investigated in the Jurkat T cancer cell line using the whole-cell patch-clamp technique. The electrophysiological measurements were preceded by experiments assessing cell viability, and the patch-clamp data were consistent with results obtained from MTT-based assays. We observed an almost complete and irreversible inhibition of Kv1.3 in the presence of IBC. The non-prenylated chalcones also inhibited the channels, but with lower potency and in a reversible and incomplete manner. The inhibitory effect of IBC was significantly enhanced upon co-application with simvastatin (SIM) and mevastatin (MEV). In contrast, inhibition by the non-prenylated chalcones was significantly increased only in the presence of mevastatin, but not simvastatin. The channel inhibition may be related to the anti-proliferative and pro-apoptotic activities of these compounds in Kv1.3-expressing cancer cells. Altogether, our results indicate that both prenylated and non-prenylated chalcones, particularly in combination with statins, may represent biologically active scaffolds, warranting further optimization and preclinical evaluation. Full article

Background: Xanthohumol (XN), a prenylated chalcone flavonoid derived from hops (Humulus lupulus), is increasingly recognized as a highly pleiotropic natural compound. Objective: We aimed to structure XN’s mechanistic hierarchy with emerging translational relevance across disease areas. Methods: We performed a comprehensive and integrative literature review of XN for its biological and translational effects across cancer, metabolic, neurological, cardiovascular, hepatic, renal, and dermatological disorders. Results: Mechanistically, XN exerts diverse bioactivities by inhibiting major pro-oncogenic and pro-inflammatory pathways, such as NF-κB, PI3K/Akt/mTOR, STAT3, HIF-1α, and selective MAPK cascades, while activating cytoprotective signaling, such as the Nrf2/ARE and AMPK pathways. Through these coordinated actions, XN modulates redox homeostasis, mitochondrial integrity, apoptosis, autophagy, ferroptosis, and inflammatory responses. In oncology, XN demonstrates broad-spectrum anticancer activity in preclinical models by inhibiting proliferation; inducing cell cycle arrest and apoptosis; suppressing epithelial–mesenchymal transition, angiogenesis, and metastasis; and restoring chemosensitivity in resistant cancers, including breast, lung, gastric, liver, and head-and-neck carcinomas. Beyond cancer, XN exhibits multi-organ protective bioactivities through antioxidative, antimicrobial, antiviral, and anti-inflammatory activities; inhibition of ferroptosis and excitotoxicity; and preservation of mitochondrial integrity. It shows beneficial effects in preclinical models of Parkinson’s disease, Alzheimer’s disease, hepatic steatosis and fibrosis, renal ischemia–reperfusion injury, cardiovascular dysfunction, skin photoaging, and atopic dermatitis. Human subject studies demonstrate that XN is safe and well tolerated, with observed reductions in oxidative DNA damage and inflammatory cytokine release. Recent advances in micellar formulations have improved XN’s systemic bioavailability and thus its translational feasibility. Conclusions: In summary, XN is a safe, multifunctional natural compound with strong potential for modulating disease-relevant biological pathways associated with cancer, neurodegenerative diseases, metabolic disorders, and inflammatory skin conditions. Continued efforts to enhance its bioavailability and conduct rigorous clinical trials are essential to fully establish its clinical relevance in patient populations. Full article

Prenylated chalcones, a subclass of chalcones distinguished by the addition of one or more prenyl (3-methylbut-2-enyl) groups, have attracted significant attention due to their promising biological activities. The origins, chemical diversity, and synthetic routes used to prepare naturally occurring and synthetic prenylated chalcones are discussed in this review paper, alongside their diverse pharmacological properties, as reported over the past 10 years (2015–2025), mainly emphasising their strong anti-cancer, anti-inflammatory, anti-bacterial, anti-fungal, anti-parasitic, and anti-malarial effects. We address their structure–activity relationships (SARs) to interrogate how prenylation affects the pharmacological activity of these chalcones. 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

Prenylation increases the structural diversity and biological activity of flavonoids. In this study, an aromatic prenyltransferase, FgPT1, was identified from Fusarium globosum. This enzyme was demonstrated to specifically catalyze the prenylation of flavanones, including naringenin, hesperitin, eriodictyol, liquiritigenin, rac-pinocembrin, and dihydrogenistein, and exhibited no activity toward other types of flavonoids, including chalcones, flavonols, isoflavonoids, and flavonols. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and nuclear magnetic resonance (NMR) analysis indicated that the majority of prenylated products were 6-C prenyl flavanones, with the exception of liquiritigenin, which was additionally transformed to 4′-O prenyl liquiritigenin. Enzyme kinetic analysis suggested that FgPT1 exhibited the highest catalytic efficiency towards naringenin, with a k_cat/K_M value determined as 61.92 s⁻¹ M⁻¹, and the lowest catalytic efficiency towards liquiritigenin, with a k_cat/K_M of 1.18 s⁻¹ M⁻¹. Biochemical characterization suggested that FgPT1 functioned as a metal-dependent enzyme with optimal activity in the presence of Ba²⁺ at pH 7.5 and 30 °C. Site-directed mutagenesis resulted in a series of mutants, including A325V with impaired prenylation activity and V116I, V181I, and V194I with enhanced activity. V194I displayed the highest enzymatic activity with a nine-fold increase compared to wild-type FgPT1. Full article

This study investigates the anticancer potential of isocordoin, a prenylated chalcone found in Adesmia balsamica. In vitro assays on colorectal (HT-29), breast (MCF-7) and prostate (PC-3) cancer cell lines, together with a non-cancerous colon cell line (CoN CCD841), revealed that isocordoin is cytotoxic, with PC-3 and MCF-7 cells showing the highest sensitivity. The selectivity index was higher for PC-3 (5.2) than for MCF-7 (3.7) and HT-29 (2.9). Isocordoin induced morphological changes suggestive of apoptosis in tumor cells. Mechanistic studies on HT-29 and MCF-7 lines indicated that isocordoin might possess antioxidant properties while promoting the loss of mitochondrial membrane potential and caspases activation. Molecular docking showed a favorable interaction of isocordoin with caspase-3, which could explain its apoptotic effects. In silico predictions suggest that isocordoin has drug-like properties, including good absorption and permeability to the blood-brain barrier. The presence of the prenyl chain in isocordoin appears crucial for cytotoxic activity, supported by its higher lipophilicity and better interaction with caspase-3 compared to non-prenylated 2′,4′-dihydroxychalcone. Overall, isocordoin demonstrates promising anticancer activity, warranting further investigation as a potential therapeutic agent. Full article

Prostate cancer remains a significant global health concern, prompting ongoing exploration of novel therapeutic agents. Licochalcone A, a natural product in the chalcone family isolated from licorice root, is characterized by its enone structure and demonstrates antiproliferative activity in the micromolar range across various cell lines, including prostate cancer. Building on our prior success in enhancing curcumin’s antiproliferative potency by replacing the substituted phenol with a 1-alkyl-1H-imizadol-2-yl moiety, we applied a similar approach to design a new class of licochalcone A-inspired chalcones. The synthesis of these target chalcones involved key [3,3]-sigmatropic rearrangement of aryl prenyl ethers and Claisen–Schmidt condensations, yielding three derivative series. These compounds were evaluated for antiproliferative activity in both androgen receptor (AR)-positive and AR-null prostate cancer cell models using WST-1 cell proliferation assay. Systematic evaluation of licochalcone A across four prostate cancer cell lines indicated a modest advantage over enzalutamide, an FDA-approved AR antagonist, in suppressing 22Rv1 cell proliferation. Interestingly, three ester derivatives by replacing the phenol next to the carbonyl with an alkoxide demonstrated similar antiproliferative potency to licochalcone A in both AR-positive and AR-negative prostate cancer cell lines. This suggests that the phenol moiety on licochalcone A may be a promising site for chemical manipulations to enhance anti-prostate cancer activity. Among the synthesized chalcones, nine derivatives showed improved selectivity for AR-positive LNCaP and 22RV1 cells relative to AR-negative PC-3 and DU145 cells, surpassing licochalcone A in selectivity. Additionally, the antiproliferative potency was highly dependent on the R group attached to the imidazole. Most of the derivatives showed antiproliferative potency against androgen receptor-positive LNCaP and 22Rv1 cells, comparable to that of enzalutamide and licochalcone A. These findings suggest that optimization of licochalcone A-inspired chalcones as potential anti-prostate cancer agents warrants further investigation. Full article

Xanthohumol, a prenylated chalcone in the flavonoid group, naturally occurs in many plants and exhibits antioxidant, anticancer, anti-inflammatory, antibacterial, and antiviral effects. The growing interest in xanthohumol due to its potential therapeutic properties has led to the increase in the pool of products available on the market. The novelty of this study is the proposal of a rapid and cost-effective procedure useful for performing quality control on products containing xanthohumol in the form of dietary supplements and cosmetics as well as testing their stability. For this purpose, the thin-layer chromatography method with densitometric detection was used, which was validated in accordance with ICH (International Conference on Harmonization) guidelines. The mobile phase was toluene, 1,4-dioxane, and glacial acetic acid (37:10:1.5 v/v/v), and TLC silica gel 60 F₂₅₄ plates were used as the stationary phase. The validation process assessed linearity, with a correlation coefficient (r) of 0.9987. The calculated LOD (limit of detection) and LOQ (limit of quantification) values were 3.82 and 11.57 ng/spot, respectively. Accuracy was evaluated by determining percentage recovery at three concentration levels (80, 100, and 120%), with an average recovery of 100% and RSD below 1%, confirming good accuracy. Precision was indicated by an RSD of less than 2.20%. The average content of xanthohumol in dietary supplements ranged from about 8 to 29% of the content declared by the manufacturers. The stability tests showed that XN decomposes most slowly in water (t_0.5 = 10.86 h) compared with acidic (t_0.5 = 10.80 h) and alkaline solutions (t_0.5 = 7.39 h), as well as in the presence of an oxidizing agent (t_0.5 = 18.38 h), at all tested temperatures, which is confirmed by the calculated kinetic parameters. In the tests of antioxidant capacity, xanthohumol shows significantly higher radical scavenging capacity than vitamin C in the entire range of analyzed concentrations (0.03–2.40 mmol/L). Full article

Xanthohumol (1) is a major prenylated flavonoid in hops (Humulus lupulus L.) which exhibits a broad spectrum of health-promoting and therapeutic activities, including anti-inflammatory, antioxidant, antimicrobial, and anticancer effects. However, due to its lipophilic nature, it is poorly soluble in water and barely absorbed from the gastrointestinal tract, which greatly limits its therapeutic potential. One method of increasing the solubility of active compounds is their conjugation to polar molecules, such as sugars. Sugar moiety introduced into the flavonoid molecule significantly increases polarity, which results in better water solubility and often leads to greater bioavailability. Entomopathogenic fungi are well known for their ability to catalyze O-glycosylation reactions. Therefore, we investigated the ability of selected entomopathogenic filamentous fungi to biotransform xanthohumol (1). As a result of the experiments, one aglycone (2) and five glycosides (3–7) were obtained. The obtained (2″E)-4″-hydroxyxanthohumol 4′-O-β-D-(4‴-O-methyl)-glucopyranoside (5) has never been described in the literature so far. Interestingly, in addition to the expected glycosylation reactions, the tested fungi also catalyzed chalcone–flavanone cyclization reactions, which demonstrates chalcone isomerase-like activity, an enzyme typically found in plants. All these findings undoubtedly indicate that entomopathogenic filamentous fungi are still an underexploited pool of novel enzymes. Full article

Xanthohumol (Xn), a prenylated chalcone found in Hop (Humulus lupulus L.), has been shown to have potent anti-aging, diabetes, inflammation, microbial infection, and cancer properties. Unfortunately, this molecule has undesirable characteristics such as inadequate intake, low aqueous solubility, and a short half-life. To address these drawbacks, researchers have made numerous attempts to improve its absorption, solubility, and bioavailability. Polymeric drug delivery systems (PDDSs) have experienced significant development over the last two decades. Polymeric drug delivery is defined as a formulation or device that allows the introduction of a therapeutic substance into the body. Biodegradable and bioreducible polymers are the ideal choice for a variety of new DDSs. Xn formulations based on biodegradable polymers and naturally derived compounds could solve some of the major drawbacks of Xn-based drug delivery. In this regard, the primary concern of this study is on presenting innovative formulations for Xn delivery, such as nanoparticles (NPs), nanomicelles, nanoliposomes, solid lipid nanoparticles (SLNs), and others, as well as the received in vitro and in vivo data. Furthermore, this work describes the chemistry and broad biological activity of Xn, which is particularly useful in modern drug technology as well as the cosmetics industry. It is also important to point out that the safety of using Xn, and its biotransformation, pharmacokinetics, and clinical applications, have been thoroughly explained in this review. Full article

Angelica keiskei Koidzumi (A. keiskei) is used as a traditional medicine, anti-aging agent, and health food, as well as to restore vitality. Xanthoangelol (xanol), a prenylated chalcone, is the predominant constituent of A. keiskei. Oral squamous cell carcinoma (OSCC), the most common malignancy, has a high proliferation rate and frequent metastasis. However, it is unknown whether xanol has anti-OSCC effects on apoptosis, autophagy, and necroptosis. In the present study, we purified xanol from A. keiskei and demonstrated that it suppressed cell proliferation and induced cytotoxicity in human OSCC. Xanol triggered apoptotic cell death by regulating apoptotic machinery molecules but inhibited necroptotic cell death by dephosphorylating the necroptotic machinery molecules RIP1, RIP3, and MLKL in human OSCC. We also found that xanol inhibited the PI3K/AKT/mTOR/p70S6K pathway and induced autophagosome formation by enhancing beclin-1 and LC3 expression levels and reducing p62 expression levels. Furthermore, we showed that xanol prevented the metastatic phenotypes of human OSCC by inhibiting migration and invasion via the reduction of MMP13 and VEGF. Finally, we demonstrated that xanol exerted anticancer effects on tumorigenicity associated with its transformed properties. Taken together, these findings demonstrate the anticancer effects and biological mechanism of action of xanol as an effective phytomedicine for human OSCC. Full article

Hop cones are well-known for their antimicrobial properties, attributed to their specialized metabolites. Thus, this study aimed to determine the in vitro antifungal activity of different hop parts, including by-products such as leaves and stems, and some metabolites against Venturia inaequalis, the causal agent of apple scab. For each plant part, two types of extracts, a crude hydro-ethanolic extract and a dichloromethane sub-extract, were tested on spore germination of two strains with different sensitivities to triazole fungicides. Both extracts of cones, leaves and stems were able to inhibit the two strains, whereas rhizomes did not show activity. The apolar sub-extract of leaves appeared as the most active modality tested with half maximal inhibitory concentrations (IC₅₀) of 5 and 10.5 mg·L⁻¹ on the sensitive strain and the strain with reduced sensitivity, respectively. Differences in activity level between strains were noticed for all active modalities tested. Sub-extracts of leaves were then separated into seven fractions by preparative HPLC and tested on V. inaequalis. One fraction, containing xanthohumol, was especially active on both strains. This prenylated chalcone was then purified by preparative HPLC and showed significant activity against both strains, with IC₅₀ of 1.6 and 5.1 mg·L⁻¹. Therefore, xanthohumol seems to be a promising compound to control V. inaequalis. Full article

Flavonoids and chalcones are known for their manifold biological activities, of which many affect the central nervous system. Pyranochalcones were recently shown to have a great neurogenic potential, which is partly due to a specific structural motif-the pyran ring. Accordingly, we questioned if other flavonoid backbones with a pyran ring as structural moiety would also show neurogenic potential. Different semi-synthetic approaches starting with the prenylated chalcone xanthohumol, isolated from hops, led to pyranoflavanoids with different backbones. We identified the chalcone backbone as the most active backbone with pyran ring using a reporter gene assay based on the promoter activity of doublecortin, an early neuronal marker. Pyranochalcones therefore appear to be promising compounds for further development as a treatment strategy for neurodegenerative diseases. Full article

The antiproliferative activity of xanthohumol (1), a major prenylated chalcone naturally occurring in hops, and its aurone type derivative (Z)-6,4′-dihydroxy-4-methoxy-7-prenylaurone (2) were investigated. Both flavonoids, as well as cisplatin as a reference anticancer drug, were tested in vivo against ten human cancer cell lines (breast cancer (MCF-7, SK-BR-3, T47D), colon cancer (HT-29, LoVo, LoVo/Dx), prostate cancer (PC-3, Du145), lung cancer (A549) and leukemia (MV-4-11) and two normal cell lines (human lung microvascular endothelial (HLMEC)) and murine embryonic fibroblasts (BALB/3T3). Chalcone 1 and aurone 2 demonstrated potent to moderate anticancer activity against nine tested cancer cell lines (including drug-resistant ones). The antiproliferative activity of all the tested compounds against cancer and the normal cell lines was compared to determine their selectivity of action. Prenylated flavonoids, especially the semisynthetic derivative of xanthohumol (1), aurone 2, were found as selective antiproliferative agents in most of the used cancer cell lines, whereas the reference drug, cisplatin, acted non-selectively. Our findings suggest that the tested flavonoids can be considered strong potential candidates for further studies in the search for effective anticancer drugs. Full article

Many natural products with greater therapeutic efficacy are limited to target several chronic diseases such as cancer, diabetes, and neurodegenerative diseases. Among the natural products from hops, i.e., Xanthohumol (XH), is a prenylated chalcone. The present research work focuses on the enhancement of the poor oral bioavailability and weak pharmacokinetic profile of XH. We exemplified the development of a Xanthohumol-loaded solid lipid nanoparticles (XH-SLNs) cargo system to overcome the limitations associated with its bioavailability. The XH-SLNs were prepared by a high-shear homogenization/ultrasonication method and graphical, numerical optimization was performed by using Box–Behnken Design. Optimized XH-SLNs showed PS (108.60 nm), PDI (0.22), ZP (−12.70 mV), %EE (80.20%) and an amorphous nature that was confirmed by DSC and PXRD. FE-SEM and HRTEM revealed the spherical morphology of XH-SLNs. The results of release studies were found to be 9.40% in 12 h for naive XH, whereas only 28.42% of XH was released from XH-SLNs. The slow release of drugs may be due to immobilization of XH in the lipid matrix. In vivo pharmacokinetic study was performed for the developed XH-SLNs to verify the enhancement in the bioavailability of XH than naive XH. The enhancement in the bioavailability of the XH was confirmed from an increase in C_max (1.07-folds), AUC_0-t (4.70-folds), t_1/2 (6.47-folds) and MRT (6.13-folds) after loading into SLNs. The relative bioavailability of XH loaded in SLNs and naive XH was found to be 4791% and 20.80%, respectively. The cytotoxicity study of naive XH, XH-SLNs were performed using PC-3 cell lines by taking camptothecin as positive control. The results of cytotoxicity study revealed that XH-SLNs showed good cell inhibition in a sustained pattern. This work successfully demonstrated formulation of XH-SLNs with sustained release profile and improved oral bioavailability of XH with good anticancer properties against PC-3 cells. Full article