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Sophora flavescens has been widely used in traditional Chinese medicine for over 1700 years. This plant is known for its heat-clearing, damp-drying, insecticidal, and diuretic properties. Phytochemical research has identified prenylated flavonoids as a unique class of bioactive compounds in S. flavescens. Recent pharmacological studies reveal that the prenylated flavonoids from S. flavescens (PFS) exhibit potent antitumor, anti-inflammatory, and glycolipid metabolism-regulating activities, offering significant therapeutic benefits for various diseases. However, the pharmacokinetics and toxicological profiles of PFS have not been systematically studied. Despite the diverse biological effects of prenylated flavonoid compounds against similar diseases, their structure-activity relationship is not yet fully understood. This review aims to summarize the latest findings regarding the chemical composition, drug metabolism, pharmacological properties, toxicity, and structure-activity relationship of prenylated flavonoids from S. flavescens. It seeks to highlight their potential for clinical use and suggest directions for future related studies. [ABSTRACT FROM AUTHOR]

Panduratin A is a prenylated flavonoid derivative from Boesenbergia pandurata with many potential biological activities. The biogenesis of this compound and its derivatives is believed to involve a Diels-Alder reaction between monoterpenoid and chalcone derivatives. This study provides insight into modeling biogenesis through the Diels-Alderreaction for Panduratin A and derivatives biosynthesis. We are using M06-2X/6-31G(d)//PM6 level of theory to explore the potential energy surfaces, asynchronicity degree, and global electron density transfer. Explicit water was applied to mimic physiological conditions. Contrary to the fact that water accelerates this reaction through hydrogen bonding catalysis, we found that water could slow this reaction. These results suggest that this reaction proceeds very slowly under physiological conditions, and enzymes catalyze this reaction.

Abstract Background Golovinomyces cichoracearum (DC.) is the main pathogen for tobacco powdery mildew fungus disease. Its outbreaks often result in severe harvest losses for the yield and quality of tobacco. Artocarpus champeden is rich in prenylated flavonoids, which are important for the plant’s defensive strategies. With the aim of continuously exploring bioactive natural metabolites for agricultural chemicals, the chemical investigations on the twigs of A. champeden were carried out. Results Six new (1–6) and five known (7–11) prenylated flavonoids were isolated. Compound 1 is the first example of flavone whose prenylated side-chain is converted into an unusual 1H-pyrrol-2-yl functional group. Compounds 2 and 3 are rare flavones bearing a 4-methylfuran-2-yl moiety. The frameworks of the above three flavones are reported in natural products for the first time. Interestingly, compound 1 showed high anti-G. cichoracearum activity with an inhibition rate of 88.3% ± 6.2. This rate is higher than that of the positive control (with an inhibition rate of 81.5% ± 6.3) compared to the negative control, compounds 2–11 also showed potential activities with inhibition rates in the range of 50.9%–72.0%. In addition, the mechanistic studies on 1 revealed that it has a potent direct effect on conidiospores of G. cichoracearum and induces systemic acquired resistance for tobacco plants, which may be the reasons for its significant effects against G. cichoracearum. Conclusions Powdery mildew is a fungal disease harmful to tobacco. Flavonoids have been identified as the sources of promising antifungal agents. For prenylated flavonoids, the combination of a flavonoid skeleton with prenylated side-chain can give the resultant more potential for biological activities. The successful isolation and structure identification of the above prenylated flavonoids provide new materials for the screening of powdery mildew inhibitors, and also contribute to the improved utilization of A. champeden. Graphical Abstract

Humulus lupulus L. - Hopfen - ist eine seit langem verwendete Arzneipflanze. Die traditionelle Anwendung bei Schlaflosigkeit hängt mit den Bittersäuren zusammen, welche den Hopfen auch für die Brauindustrie wertvoll machen. Mit Hilfe einer aktivitätsgeführten Fraktionierung zur Bestimmung der differenzierungsinduzierenden Aktivität in neuronalen Vorläuferzellen der Maus wurde Xanthohumol C als potentes neuroregeneratives Chalkon identifiziert. Substanzen mit diesem Wirkprofil eignen sich zur Behandlung von neurodegenerativen Erkankungen, welche aufgrund des demogaphischen Wandels eine zunehmende Bürde der westlichen Gesellschaft darstellen. Der Chroman-Ring des Xanthohumol C wurde als wichtiges Strukturmerkmal für die Wirksamkeit identifiziert. Ein auf Cyclodextrinen basiertes Extraktionsverfahren, welches zu einer besser wasserlöslichen und bioverfügbaren Formulierung führt, ebnet den Weg für mögliche phytopharmazeutische Anwendungen des Hopfens im Bereich der Neuroregeneration.

Panduratin A is a prenylated flavonoid derivative from Boesenbergia pandurata with many potential biological activities. The biogenesis of this compound and its derivatives is believed to involve a Diels-Alder reaction between monoterpenoid and chalcone derivatives. This study provides insight into modeling biogenesis through the Diels-Alder reaction for Panduratin A and derivatives biosynthesis. We are using M06-2X/6-31G(d)//PM6 level of theory to explore the potential energy surfaces, asynchronicity degree, and global electron density transfer. Explicit water was applied to mimic physiological conditions. Contrary to the fact that water accelerates this reaction through hydrogen bonding catalysis, we found that water could slow this reaction. These results suggest that this reaction proceeds very slowly under physiological conditions, and enzymes catalyze this reaction. [ABSTRACT FROM AUTHOR]

Background: Golovinomyces cichoracearum (DC.) is the main pathogen for tobacco powdery mildew fungus disease. Its outbreaks often result in severe harvest losses for the yield and quality of tobacco. Artocarpus champeden is rich in prenylated flavonoids, which are important for the plant's defensive strategies. With the aim of continuously exploring bioactive natural metabolites for agricultural chemicals, the chemical investigations on the twigs of A. champeden were carried out. Results: Six new (1–6) and five known (7–11) prenylated flavonoids were isolated. Compound 1 is the first example of flavone whose prenylated side-chain is converted into an unusual 1H-pyrrol-2-yl functional group. Compounds 2 and 3 are rare flavones bearing a 4-methylfuran-2-yl moiety. The frameworks of the above three flavones are reported in natural products for the first time. Interestingly, compound 1 showed high anti-G. cichoracearum activity with an inhibition rate of 88.3% ± 6.2. This rate is higher than that of the positive control (with an inhibition rate of 81.5% ± 6.3) compared to the negative control, compounds 2–11 also showed potential activities with inhibition rates in the range of 50.9%–72.0%. In addition, the mechanistic studies on 1 revealed that it has a potent direct effect on conidiospores of G. cichoracearum and induces systemic acquired resistance for tobacco plants, which may be the reasons for its significant effects against G. cichoracearum. Conclusions: Powdery mildew is a fungal disease harmful to tobacco. Flavonoids have been identified as the sources of promising antifungal agents. For prenylated flavonoids, the combination of a flavonoid skeleton with prenylated side-chain can give the resultant more potential for biological activities. The successful isolation and structure identification of the above prenylated flavonoids provide new materials for the screening of powdery mildew inhibitors, and also contribute to the improved utilization of A. champeden. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC), or liver cancer, is the fourth largest cancer in Indonesia, with 21,392 new cases and around 20,920 deaths. One of the standard drugs for liver cancer patients is lenvatinib, but lenvatinib has dangerous side effects such as hypertension. Previous studies reported that jackfruit root extract (Artocarpus heterophyllus Lam.) contains prenylated flavonoid compounds known to have anticancer activity. This study aims to find compounds that have the potential to the anticancer liver from jackfruit root by understanding the interaction between prenylated flavonoid derivative compounds against the VEGFR2 receptor (PDB ID: 3WZE) in silico. The methods include toxicity and pharmacokinetic screening, drug scanning, docking, and molecular dynamics simulation. The toxicity, pharmacokinetic, and drug scans of cycloartocarpesin are better than lenvatinib. The docking cycloartocarpesin compound showed ∆G -8.49 kcal/mol and Ki 0.59967 M lower than lenvatinib by forming the same hydrogen bond at residue Glu885. The molecular dynamics simulation of the cycloartocarpesin compound in the MM-GBSA calculation method resulted in a ∆Gtotal of -56.641 kcal/mol. The cycloartocarpesin compound is predicted to be used as a candidate for liver anticancer drugs because it has better stability and affinity than lenvatinib.

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health threat. Traditional herbals and dietary plants with medicinal values have a long antiviral history and, thus, are extensively studied in COVID-19 therapeutics development. Breadfruit (Artocarpus altilis) is a food crop with rich nutrient composition. This study screened selected breadfruit prenylated flavonoids for their potential inhibitory activities against the SARS-CoV family receptors using molecular docking and molecular dynamics (MD) simulation. The A. altilis prenylated flavonoids were selected as target ligands (artocarpin, artoindonesianin V, artonin M, cudraflavone A and cycloartobiloxanthone) and molecular targets from the SARS-CoV family were designated as receptors. Molecular docking was applied with the Lamarckian Genetic algorithm to measure the receptor-ligand orientation using AutoDock Vina software. The structural interactions of the receptor-ligand complexes were visualised using the Biovia Discovery Studio 4.5. Under all possible receptor-ligand combinations, the complexes' minimum binding affinities (MBA) ranged from -5.5 to -9.1 kcal/mol and held by hydrophobic interactions, hydrogen bonds and electrostatic attractions. Receptor-ligand complexes with the least MBA (<-6.0 kcal/mol) along with strong structural interactions were validated by MD simulation using the GROMACS software. The 5RE4-artocarpin and 5RE4-artoindonesianin V showed the highest hydrophobic interactions at MBA=-6.6 kcal/mol and -6.4 kcal/mol, respectively. The trajectory analysis of 5RE4-artocarpin and 5RE4-artoindonesianin V complexes was fairly stable throughout a 50 ns MD simulation run. The findings conclude that artocarpin and artoindonesianin V are good potential SARS-CoV family receptor inhibitors. [ABSTRACT FROM AUTHOR]

Compounds with lifespan extension activity are rare, although increasing research efforts have been invested in this field to find ways to extend healthy lifespan. By applying a yeast-based high-throughput assay to identify the chronological lifespan extension activity of mulberry extracts rapidly, we demonstrated that a group of prenylated flavones, particularly morusin and mulberrin, could extend the chronological lifespan of budding yeast via a nutrient-dependent regime by at least partially targeting SCH9. Their antiaging activity could be extended to C. elegans by promoting its longevity, dependent on the full functions of genes akt-1 or akt-2. Moreover, additional benefits were observed from morusin- and mulberrin-treated worms, including increased reproduction without the influence of worm health (pumping rate, pumping decline, and reproduction span). In the human HeLa cell model, morusin and mulberrin inhibited the phosphorylation of p70S6K1, promoted autophagy, and slowed cell senescence. The molecular docking study showed that mulberrin and morusin bind to the same pocket of p70S6K1. Collectively, our findings open up a potential class of prenylated flavones performing their antiaging activity via nutrient-sensing pathways. [ABSTRACT FROM AUTHOR]

Prenylated flavonoids are the primary modification of flavonoids and exhibit a diverse range of physiological activities. In this study, a co-immobilization of two-enzyme cascade was developed to regenerate dimethylallyl diphosphate (DMAPP). Shigella flexneri promiscuous kinase (SfPK) and Methanolobus tindarius isopentenyl phosphate kinase (MtIPK) were immobilized onto carboxymethyl cellulose magnetic nanoparticles (CMN) with a maximum load of 0.35 mg/mg and 0.28 mg/mg, respectively. The optimal activity of CMN-SfPK and CMN-MtIPK were at pH 9.5 and 55°C, and pH 7.0 and 35 °C, respectively. CMN-SfPK and CMN-MtIPK exhibited superior catalytic efficiency compared to free enzymes. CMN-SfPK was coupled with CMN-MtIPK to develop an efficient DMAPP regeneration system from prenol. Subsequently, SfPK, MtIPK and Aspergillus fumigatus prenyltransferase (AfPT) were co-immobilized on CMN to form CMN-SfPK-MtIPK-AfPT (CSMA) according to the optimal ratio. The 3'-C-prenylnaringenin production rate in CSMA reached 0.37 mmol/L/h, which was 1.85 times that of single-immobilized enzymes. Finally, the total production and production rate of 3'-C-prenylnaringenin in CSMA reached 2.55 mM and 0.255 mmol/L/h with 10 cycles. Therefore, the method described herein for efficient production of DMAPP and 3'-C-prenylnaringenin by using co-immobilized enzymes can be widely used for the prenylation of flavonoids. [Display omitted] • An efficient DMAPP regeneration pathway was successfully developed. • Co-immobilization of three-enzyme system for the one-pot synthesis of prenylated flavonoids. • The production rate in CSMA was 1.85 times that of single-immobilized enzymes. • The total production of 3'-C-prenylnaringenin in CSMA reached 2.55 mM. • CSMA provides a novel strategy for low-cost preparation of prenylated flavanoids. [ABSTRACT FROM AUTHOR]

Six new prenylated flavonoids, named visconaeas A-F (1–6), and eleven known isopentenyl flavonoids (7–17) were isolated from Dodonaea viscosa (L.) Jacq. The structures of the separated compounds were determined through comprehensive spectral analysis and quantum chemical calculations. These compounds were tested for their anti-Zika virus and cytotoxicity activities. The results indicated that compound 4 showed low cytotoxicity and strong anti-Zika virus potential with EC 50 16.34 μM. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: Bituminaria bituminosa is a medicinal plant recognized for its phytochemicals, such as furanocoumarins, pterocarpans, and flavonoids. Since the secondary metabolism is influenced by the plant-endophyte interactions, the endophytic bacterial community of B. bituminosa was explored and the possible interactions with the plant were described. Materials and methods: Different bacterial strains were isolated from different organs of in vitro plants as shoots, roots, and seeds. The bacterial strains were identified and phenotypically characterized for different traits; strains were also exposed to different concentrations of B. bituminosa plant extract showing different susceptibility, probably determined by different secondary metabolites produced by the plant in the different organs (i.e. aerial parts and roots). Results and discussion: Bacterial strains showed different phenotypic characteristics; the 6 detected haplotypes were dominated by a single species related to Stenotrophomonas rhizophila. Endophytes isolated from the aerial parts produced a higher indole-3-acetic acid (IAA) amount than those of the roots, while all strains were unable to produce biosurfactants and antagonistic activity toward the other strains. The research opens new perspectives for future analysis addressed to test the susceptibility of the endophytic bacterial community of B. bituminosa toward the pure compounds extracted from the plants, and to investigate the role of these compounds on the distribution of endophytes within the different plant tissues. [ABSTRACT FROM AUTHOR]

Two new flavonoids, 8,2′-diprenyl-3,5,7,5′-tetrahydroxyflavone (1) and 8-(1-methoxy-2,3-dihydroxy-3-methylbutyl)naringenin (2), along with twelve known compounds (3–14), were isolated from the leaves of Macaranga pustulata. The structures of the new compounds 1 and 2 were established by detailed spectroscopic data analysis and ECD computational methods. The inhibitory effects of compounds 1–6 against NLRP3 inflammasome activation as well as the cytotoxic activities of compounds 1–4 against MCF-7 and HCT-116 cancer cell lines were investigated. Compound 3 showed weak cytotoxicity against HCT-116 (IC50 = 55.747 ± 3.212 μM). [ABSTRACT FROM AUTHOR]

Medicinal plants are known as sources of potential antimicrobial compounds belonging to different classes. The aim of the present work was to evaluate the antimicrobial potential of the crude extract, fractions, and some isolated secondary metabolites from the leaves of Macaranga occidentalis, a Cameroonian medicinal plant traditionally used for the treatment of microbial infections. Repeated column chromatography of the ethyl acetate and n-butanol fractions led to the isolation of seventeen previously known compounds (1−17), among which three steroids (1−3), one triterpene (4), four flavonoids (5−8), two stilbenoids (9 and 10) four ellagic acid derivatives (11−14), one geraniinic acid derivative (15), one coumarine (16), and one glyceride (17). Their structures were elucidated mainly by means of extensive spectroscopic and spectrometric (1D and 2D NMR and, MS) analysis and comparison with the published data. The crude extract, fractions, and isolated compounds were all screened for their antimicrobial activity. None of the natural compounds was active against Candida strains. However, the crude extract, fractions, and compounds showed varying levels of antibacterial properties against at least one of the tested bacterial strains, with minimal inhibitory concentrations (MICs) ranging from 250 to 1000 μg/mL. The n-butanol (n-BuOH) fraction was the most active against Escherichia coli ATCC 25922, with an MIC value of 250 μg/mL. Among the isolated compounds, schweinfurthin B (10) exhibited the best activity against Staphylococcus aureus NR 46003 with a MIC value of 62.5 μg/mL. In addition, schweinfurthin O (9) and isomacarangin (6) also exhibited moderate activity against the same strain with a MIC value of 125 μg/mL. Therefore, pharmacomodulation was performed on compound 6 and three new semisynthetic derivatives (6a–c) were prepared by allylation and acetylation reactions and screened for their in vitro antimicrobial activity. None of the semisynthetic derivatives showed antimicrobial activity against the same tested strains. The chemophenetic significance of the isolated compounds is also discussed in this paper. [ABSTRACT FROM AUTHOR]

Prenylated flavonoids show antibacterial activity towards Staphylococcus aureus (S. aureus). Previous studies have suggested that the prenyl side-chain is an important active group for antimicrobial activity. However, prenylated flavonoids also often contain a pyran ring isopentene group. Few studies have explored the contribution of the pyran ring isopentene group to antibacterial activity. In this study, the antibacterial activities of structurally related flavonoid compounds from mulberry root bark were studied by detecting the minimum inhibitory concentration (MIC) and colony counting. These flavonoid compounds all exhibited antibacterial activities against S. aureus ATCC6538, S. aureus ATCC25923 and methicillin-resistant S. aureus (MRSA) ATCC43300 with MIC values of 7.3–248.2 μmol/L, 7.3–330.9 μmol/L, and 7.3–330.9 μmol/L, respectively. Structure-activity relationship analyses demonstrated that the pyran ring isopentene group plays an important role in antibacterial activity. Thus, the pyran ring isopentene group is an overlooked antimicrobial active group in prenylated flavonoids. [ABSTRACT FROM AUTHOR]

Epimedium pubescens is a species of the family Berberidaceae in the basal eudicot lineage, and a main plant source for the traditional Chinese medicine “Herba Epimedii”. The current study achieved a chromosome-level genome assembly of E. pubescens with the genome size of 3.34 Gb, and the genome guided discovery of a key prenyltransferase (PT) in E. pubescens. Our comparative genomic analyses confirmed the absence of Whole Genome Triplication (WGT-γ) event shared in core eudicots and further revealed the occurrence of an ancient Whole Genome Duplication (WGD) event approximately between 66 and 81 Million Years Ago (MYA). In addition, whole genome search approach was successfully applied to identify 19 potential flavonoid PT genes and an important flavonoid PT (EpPT8) was proven to be an enzyme for the biosynthesis of medicinal compounds, icaritin and its derivatives in E. pubescens. Therefore, our results not only provide a good reference genome to conduct further molecular biological studies in Epimedium genus, but also give important clues for synthetic biology and industrial production of related prenylated flavonoids in future. [ABSTRACT FROM AUTHOR]

With the abuse of antibiotics, bacterial antibiotic resistance is becoming a major public healthcare issue. Natural plants, especially traditional Chinese herbal medicines, which have antibacterial activity, are important sources for discovering potential bacteriostatic agents. This study aimed to develop a fast and reliable method for screening out antimicrobial compounds targeting the MRSA membrane from Psoralea corylifolia Linn. seed. A UPLC-MS/MS method was applied to identify the prenylated flavonoids in major fractions from the extracts of Psoralea corylifolia Linn. seed. The broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of different fractions and compounds. The morphological and ultrastructural changes of MRSA were determined by scanning electron microscopy (SEM). The membrane-targeting mechanism of the active ingredients was explored by membrane integrity assays, membrane fluidity assays, membrane potential assays, ATP, and ROS determination. We identified eight prenylated flavonoids in Psoralea corylifolia Linn. seed. The antibacterial activity and mechanism studies showed that this type of compound has a unique destructive effect on MRSA cell membranes and does not result in drug resistance. The results revealed that prenylated flavonoids in Psoralea corylifolia Linn. seeds are promising candidates for the development of novel antibiotic agents to combat MRSA-associated infections. [ABSTRACT FROM AUTHOR]

Six new prenylated flavonoid glycosides, including four new furan-flavonoid glycosides wushepimedoside A–D (1 – 4) and two new prenyl flavonoid derivatives wushepimedoside E–F (5 – 6), and one know analog epimedkoreside B (7) were isolated from biotransformation products of the aerial parts of Epimedium wushanense. Their structures were elucidated according to comprehensive analysis of HR-MS and NMR spectroscopic data, and the absolute configurations were assigned using experimental and calculated electronic circular dichroism (ECD) data. The regulatory activity of compounds 1 – 7 on the production of testosterone in primary rat Leydig cells were investigated, and 4 and 5 exhibited testosterone production-promoting activities. Molecular docking analysis suggested that bioactive compounds 4 and 5 showed the stable binding with 3 β -HSD and 4 also had good affinity with Cyp17A1, which suggested that these compounds may regulate testosterone production through stimulating the expression of the above two key proteins. [ABSTRACT FROM AUTHOR]

The review presents prenylated flavonoids as potential therapeutic agents for the treatment of topical skin infections and wounds, as they can restore the balance in the wound microenvironment. A thorough two-stage search of scientific papers published between 2000 and 2022 was conducted, with independent assessment of results by two reviewers. The main criteria were an MIC (minimum inhibitory concentration) of up to 32 µg/mL, a microdilution/macrodilution broth method according to CLSI (Clinical and Laboratory Standards Institute) or EUCAST (European Committee on Antimicrobial Susceptibility Testing), pathogens responsible for skin infections, and additional antioxidant, anti-inflammatory, and low cytotoxic effects. A total of 127 structurally diverse flavonoids showed promising antimicrobial activity against pathogens affecting wound healing, predominantly Staphylococcus aureus strains, but only artocarpin, diplacone, isobavachalcone, licochalcone A, sophoraflavanone G, and xanthohumol showed multiple activity, including antimicrobial, antioxidant, and anti-inflammatory along with low cytotoxicity important for wound healing. Although prenylated flavonoids appear to be promising in wound therapy of humans, and also animals, their activity was measured only in vitro and in vivo. Future studies are, therefore, needed to establish rational dosing according to MIC and MBC (minimum bactericidal concentration) values, test potential toxicity to human cells, measure healing kinetics, and consider formulation in smart drug release systems and/or delivery technologies to increase their bioavailability. [ABSTRACT FROM AUTHOR]

The slow pace of discovery of bioactive natural products can be attributed to the difficulty in rapidly identifying them in complex mixtures such as plant extracts. To overcome these hurdles, we explored the utility of two machine learning techniques, i.e., Elastic Net and Random Forests, for identifying the individual anti-inflammatory principle(s) of an extract of the inflorescences of the hops (Humulus lupulus) containing hundreds of natural products. We fractionated a hop extract by column chromatography to obtain 40 impure fractions, determined their anti-inflammatory activity using a macrophage-based bioassay that measures inhibition of iNOS-mediated formation of nitric oxide, and characterized the chemical composition of the fractions by flow-injection HRAM mass spectrometry and LC-MS/MS. Among the top 10 predictors of bioactivity were prenylated flavonoids and humulones. The top Random Forests predictor of bioactivity, xanthohumol, was tested in pure form in the same bioassay to validate the predicted result (IC50 7 µM). Other predictors of bioactivity were identified by spectral similarity with known hop natural products using the Global Natural Products Social Networking (GNPS) algorithm. Our machine learning approach demonstrated that individual bioactive natural products can be identified without the need for extensive and repetitive bioassay-guided fractionation of a plant extract. [ABSTRACT FROM AUTHOR]

Hop prenylated flavonoids have been investigated for their in vivo activities due to their broad spectrum of positive health effects. Previous studies on the metabolism of xanthohumol using untargeted methods have found that it is first degraded into 8-prenylnaringenin and 6-prenylnaringenin, by spontaneous cyclisation into isoxanthohumol, and subsequently demethylated by gut bacteria. Further combinations of metabolism by hydroxylation, sulfation, and glucuronidation result in an unknown number of isomers. Most investigations involving the analysis of prenylated flavonoids used surrogate or untargeted approaches in metabolite identification, which is prone to errors in absolute identification. Here, we present a synthetic approach to obtaining reference standards for the identification of human xanthohumol metabolites. The synthesised metabolites were subsequently analysed by qTOF LC-MS/MS, and some were matched to a human blood sample obtained after the consumption of 43 mg of micellarised xanthohumol. Additionally, isomers of the reference standards were identified due to their having the same mass fragmentation pattern and different retention times. Overall, the methods unequivocally identified the metabolites of xanthohumol that are present in the blood circulatory system. Lastly, in vitro bioactive testing should be applied using metabolites and not original compounds, as free compounds are scarcely found in human blood. [ABSTRACT FROM AUTHOR]

Sophora flavescens , a traditional Chinese herb, produces a wide range of secondary metabolites with a broad spectrum of biological activities. In this study, we isolated six isopentenyl flavonoids (1-6) from the roots of S. flavescens and evaluated their activities against phytopathogenic fungi. In vitro activities showed that kurarinone and sophoraflavanone G displayed broad spectrum and superior activities, among which sophoraflavanone G displayed excellent activity against tested fungi, with EC 50 values ranging from 4.76 to 13.94 μg/mL. Notably, kurarinone was easily purified and showed potential activity against Rhizoctonia solani , Botrytis cinerea , and Fusarium graminearum with EC 50 values of 16.12, 16.55, and 16.99 μg/mL, respectively. Consequently, we initially investigated the mechanism of kurarinone against B. cinerea . It was found that kurarinone disrupted cell wall components, impaired cell membrane integrity, increased cell membrane permeability, and affected cellular energy metabolism, thereby exerting its effect against B. cinerea . Therefore, kurarinone is expected to be a potential candidate for the development of plant fungicides.

Continuation of the phytochemical investigation of the aerial parts of Tephrosia purpurea subsp. dunensis resulted in the isolation and structural elucidation of a new prenylated flavonoid demeapollinin (1), glabratephrinol (2) and a mixture (3) of tephroapollin G (3a) and epi-tephroapollin G (3b). The neuroprotective activity of compounds (1–3) besides the previously isolated compounds; dunensin (4), pseudosemiglabrin (6), glabratephrin (7), apollinin (5), kampferol 3, 7-O-α-L-dirhamnoside (8) and quercetin 3, 7-O-α-L-dirhamnoside (9) was examined. Molecular docking, acetylcholine esterase inhibitory assay and protection against both H2O2 and induced neurotoxicity were used to evaluate their neuroprotective effect. Compound 2 showed the highest acetylcholine esterase inhibitory activity (IC50 4.31 ± 0.75 µM) compared to galantamine (IC50 1.64 ± 0.32 µM), compounds 4 and 3 exhibited potent protective effect against induced neurotoxicity (IC50 7.70 ± 5.23 and 10.91 ± 6.27 µM, respectively) compared to standard epigallocatechin gallate (IC50 18.36 ± 6.22 µM). [ABSTRACT FROM AUTHOR]

Humulones and iso-humulones are potent natural antioxidants found in beer. In this study, density functional theory (DFT) method was applied for elucidating the structure-antioxidant activity relationship and molecular mechanism of antioxidant activity of eight bioactive humulones previously identified in different beer samples: isoxanthohumol, (R)- and (S)-adhumulone, cis- and trans-iso-adhumulone, cis- and trans-iso-n-humulone, and desdimethyl-octahydro-iso-cohumulone. The calculated bond dissociation enthalpies (BDEs) suggest that desdimethyl-octahydro-iso-cohumulone was the most potent compound with BDEs 5.1 and 23.9 kJ/mol lower compared to the values for resveratrol in gas phase and water, respectively. The enolic –OH is the most reactive site for hydrogen atom transfer (HAT). The presence of β-keto group with respect to enolic –OH diminishes the HAT potency via the formation of a strong intramolecular hydrogen bond. Another common antioxidant mechanism, single electron transfer followed by proton transfer (SET-PT), is only feasible for isoxanthohumol. The results of this study indicate a strong correlation between the increased antioxidant activity of beer products and the higher content of reduced iso-α-acids. [ABSTRACT FROM AUTHOR]

Abstract Background The Atlantic Forest biome extends along the entire Brazilian coast and is home to approximately 20,000 plant species, many of which are endemic; it is considered one of the hotspot regions of the planet. Several of these species are sources of natural products with biological activities that are still unknown. In this study, we evaluated the antimicrobial activity of 90 extracts derived from native Atlantic Forest tree species against Staphylococcus aureus, an important human and veterinary pathogen. Methods Extracts from native Atlantic Forest tree species were evaluated for their antimicrobial activity against S. aureus by in vitro standard methods. Phytochemical fractionation of the extract from Maclura tinctoria was performed by liquid-liquid partitioning. LC-DAD-ESI-MS was used for identification of constituents in the most active fraction. Damage of cells and alterations in the permeability of cell membrane were determined by atomic force microscopy (AFM) and crystal violet uptake assay, respectively. In vivo antimicrobial activity was evaluated using Galleria mellonella larvae infected with S. aureus with survival data collected using the Kaplan-Meier method. Results Among the organic or aqueous extracts tested here, 26 showed biological activity. Eight species showed relevant results, with a minimum inhibitory concentration (MIC) below 1 mg/mL. Antibacterial activity was registered for three species for the first time. An organic extract from Maclura tinctoria leaves showed the lowest MIC (0.08 mg/mL). Fractionation of this extract by liquid-liquid partitioning led to obtaining fraction 11FO d with a MIC of 0.04 mg/mL. This fraction showed strong activity against veterinary S. aureus isolates and contributed to the increased survival of Galleria mellonella larvae infected with S. aureus ATCC 29213. The bacterial surface was not altered by the presence of 11FO d, and no cell membrane damage was detected. The LC-DAD-ESI/MS analyses identified prenylated flavonoids as the major constituents responsible for the antibacterial activity of this active extract. Conclusion A fraction enriched in prenylated isoflavones and flavanones from M. tinctoria showed in vitro and in vivo efficacy as antistaphylococcal agents. These findings justify the need for further research to elucidate the mechanisms of action of these compounds.

Beer is an alcoholic beverage consumed worldwide, which is given its typical taste by the presence of hops. Hops contain an array technologically important substances, which are primarily represented by hop resins (humulones, lupulones, humulinones, hulupones, etc.), essential oils (humulene, myrcene, etc.) and tannins (phenolic compounds quercetin, catechin, etc.). In addition to their sensory properties, these molecules contribute to the biological and colloidal stability of beer with their antiseptic and antioxidant properties. Recently, an increased attention has been given to prenylated hop flavonoids, particularly xanthohumol, isoxanthohumol and 8- prenylnaringenin. Xanthohumol is a prenylated chalcone that exhibit antioxidant, anticancer and chemoprotective effects. Its only source in human nutrition is beer, nevertheless a large part of xanthohumol from hops is isomerized by heat to isoxanthohumol and desmethylxanthohumol, from which a racemic mixture of 6- and 8-prenylnaringenins is formed during the beer production. Xanthohumol is also converted to isoxanthohumol by digestion, leading to the formation of 8-prenylnaringenin that is being catalyzed by the enzymes of the intestinal microorganisms as well as liver enzymes. This substance is currently considered to be the most effective natural phytoestrogen. [ABSTRACT FROM AUTHOR]

The overuse of antibiotics in animal farming and aquaculture has led to multidrug-resistant methicillin-sensitive Staphylococcus aureus (MR-MSSA) becoming a common pathogen in foodborne diseases. Sophora flavescens Ait. serves as a traditional plant antibacterial agent and functional food ingredient. A total of 30 compounds ( 1 - 30 ) were isolated from the root bark of S. flavescens , consisting of 20 new compounds ( 1 - 20 ). In the biological activity assay, compound 1 demonstrated a remarkable inhibitory effect on MR-MSSA, with an MIC of 2 μg/mL. Furthermore, 1 was found to rapidly eliminate bacteria, inhibit biofilm growth, and exhibit exceptionally low cytotoxicity. Mechanistic studies have revealed that 1 possesses an enhanced membrane-targeting ability, binding to the bacterial cell membrane components phosphatidylglycerol (PG), phosphatidylethanolamine (PE), and cardiolipin (CL). This disruption of bacterial cell membrane integrity increases intracellular reactive oxygen species, protein and DNA leakage, reduced bacterial metabolism, and ultimately bacterial death. In summary, these findings suggest that compound 1 holds promise as a lead compound against MR-MSSA.

Four undescribed prenylated flavonoids, sophoratones A-D (1-4), and 17 known flavonoids, were obtained from the aerial parts of Sophora tonkinensis. Their structures with absolute configurations were elucidated by detailed interpretation of NMR spectroscopy, mass spectrometry, and ECD calculations. Meanwhile, the ability of these compounds to inhibit the release of nitric oxide (NO) by a lipopolysaccharide induced mouse in RAW 264.7 cells was assayed. The results indicated that some compounds exhibited clear inhibitory effects, with IC 50 ranging from 19.91±1.08 to 35.72±2.92 μM. These results suggest that prenylated flavonoids from the aerial parts of S. tonkinensis could potentially be used as a latent source of anti-inflammatory agents., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Hop prenylated flavonoids have been investigated for their in vivo activities due to their broad spectrum of positive health effects. Previous studies on the metabolism of xanthohumol using untargeted methods have found that it is first degraded into 8-prenylnaringenin and 6-prenylnaringenin, by spontaneous cyclisation into isoxanthohumol, and subsequently demethylated by gut bacteria. Further combinations of metabolism by hydroxylation, sulfation, and glucuronidation result in an unknown number of isomers. Most investigations involving the analysis of prenylated flavonoids used surrogate or untargeted approaches in metabolite identification, which is prone to errors in absolute identification. Here, we present a synthetic approach to obtaining reference standards for the identification of human xanthohumol metabolites. The synthesised metabolites were subsequently analysed by qTOF LC-MS/MS, and some were matched to a human blood sample obtained after the consumption of 43 mg of micellarised xanthohumol. Additionally, isomers of the reference standards were identified due to their having the same mass fragmentation pattern and different retention times. Overall, the methods unequivocally identified the metabolites of xanthohumol that are present in the blood circulatory system. Lastly, in vitro bioactive testing should be applied using metabolites and not original compounds, as free compounds are scarcely found in human blood.

Isowighteone (3’-isoprenyl genistein) is a prenylated flavonoid derivative that exhibits antibacterial, pro-apoptotic and anti-inflammatory properties. To establish a bioproduction system for this bioactive compound, hairy root cultures of pigeon pea (Cajanus cajan (L.) Millsp.) were developed via Agrobacterium rhizogenes-mediated transformation. The cultures were co-treated with methyl jasmonate, cyclodextrin, hydrogen peroxide, and magnesium chloride to enhance the production of isowighteone. The amount of isowighteone that accumulated in the culture medium upon elicitation varied with the period of elicitation. Isowighteone was purified from extracts of the culture medium by semi-preparative HPLC, and its identity was confirmed by tandem mass spectrometry. After 144 h of elicitation in 12-day-old hairy root culture, the total yield of isowighteone was 8058.618 ± 445.78 μg/g DW, of which approximately 96% was found in the culture medium. The yield of isowighteone in the elicited hairy root culture was approximately 277-fold higher than in the non-elicited root culture. The difference between the phenotypes of the elicited and non-elicited pigeon pea hairy roots was studied using scanning electron microscopy. The non-elicited hairy roots had uniform surfaces whereas the elicited roots had non-uniform shapes. Pigeon pea hairy roots provide a sustainable platform for producing and studying the biosynthesis of isowighteone.

The antiproliferative activities of 2′,3,4′,5,5′-pentahydroxy-cis-stilbene 1, resveratrol 2, oxyresveratrol 3, norartocarpetin 4, kuwanon C 5, morusin 6, cudraflavone A7, kuwanon G 8, albafuran C 9, mulberrofuran G 10, 3-acetyl-O-α-amyrin 11, 3-acetyl-O-β-amyrin 12, ursolic acid-3-O-acetate 13 and uvaol 14, previously identified from the barks of Morus nigra L., were investigated against HepG2 and MCF-7 cell lines. In addition, a series of methylated stilbenes 15–19 were prepared using compounds 1–3 and their antiproliferative effects were similarly investigated. The structure of a new 2′,3,4′-trimethoxy-5-hydroxy-trans-stilbene 19 was elucidated using spectroscopic techniques. It showed remarkable activity against MCF-7 cells with IC50 12.5 μM. However, kuwanon C (5) showed the highest antiproliferative activity with IC50 3.92 and 9.54 μM against MCF-7 and HepG2, respectively. [ABSTRACT FROM AUTHOR]

Four new prenylated flavonoids, sinoflavonoids NF–NI (1–4), were isolated from the fruits of Sinopodophyllum hexandrum by different chromatographic methods such as silica gel, Sephadex LH-20, ODS, and preparative high-performance liquid chromatography (HPLC). Their structures were elucidated on the basis of extensive spectroscopic data (UV, IR, HR-ESI-MS, 1H NMR, 13C NMR, HSQC, HMBC). [ABSTRACT FROM AUTHOR]

Four prenylated flavonoids, including isosophoranone, sophoraflavanone G, alopecurone J, alopecurone P, and a resveratrol derivative HPD (2-(4-hydroxyphenyl)-2,3-dihydrobenzo[b] furan-3,4,6-triol), were isolated from the roots of Sophora pachycarpa. The cytotoxic activity of obtained compounds was evaluated against A2780, A549, HeLa, and HCT116 human cancer cell lines. We also evaluated their histone deacetylase (HDAC) inhibitory activities. Of all compounds tested, alopecurone J was the most active with IC50 values in the range of 9.97-30.91 µM against four cancer cell lines with potent pan-HDAC inhibitory activity (IC50 = 0.08-3.85 µM). Molecular docking experiments of these compounds with HDAC8 displayed potential selective HDAC inhibitory. Molecular docking data showed consistent results in the in-vitro experiments with high selectivity towards HDAC8. The Resveratrol group plays an essential role in HDAC inhibition. [ABSTRACT FROM AUTHOR]

[Display omitted] • A thermostable prenyltransferase (AfPT) from Aspergillus fumigatiaffinis was cloned. • The expression level of AfPT reached 78.5 mU/mL by optimizing the induction conditions. • AfPT was immobilized onto carboxymethyl cellulose magnetic nanoparticles (CMN). • CMN-AfPT exhibits superior thermal stability and specific activity compared to AfPT. • CMN-AfPT maintained 68% of its original activity following 10 cycles of reuse. Prenyltransferases catalyze the synthesis of prenylated flavonoids, providing these with greater lipid solubility, biological activity, and availability. In this study, a thermostable prenyltransferase (AfPT) from Aspergillus fumigatiaffinis was cloned and expressed in Escherichia coli. By optimizing induction conditions, the expression level of AfPT reached 39.3 mU/mL, which was approximately 200 % of that before optimization. Additionally, we determined the enzymatic properties of AfPT. Subsequently, AfPT was immobilized on carboxymethyl cellulose magnetic nanoparticles (CMN) at a maximum load of 0.6 mg/mg. Optimal activity of CMN-AfPT was achieved at pH 8.0 and 55 °C. Thermostability assays showed that the residual activity of CMN-AfPT was greater than 50 % after incubation at 55 °C for 4 h. Km and Vmax of CMN-AfPT for naringenin were 0.082 mM and 5.57 nmol/min/mg, respectively. The Kcat/Km ratio of CMN-AfPT was higher than that of AfPT. Residual prenyltransferase activity of CMN-AfPT remained higher than 70 % even after 30 days of storage. Further, CMN-AfPT retained 68 % of its original activity after 10 cycles of reuse. Compared with free AfPT, CMN-AfPT showed higher catalytic efficiency, thermostability, metal ion tolerance, substrate affinity, storage stability, and reusability. Our study presents a thermostable prenyltransferase and its immobilized form for the production of prenylated flavonoids in vitro. [ABSTRACT FROM AUTHOR]

Glucokinase activators are considered as new therapeutic arsenals that bind to the allosteric activator sites of glucokinase enzymes, thereby maximizing its catalytic rate and increasing its affinity to glucose. This study was designed to identify potent glucokinase activators from prenylated flavonoids isolated from medicinal plants using molecular docking, molecular dynamics simulation, density functional theory, and ADMET analysis. Virtual screening was carried out on glucokinase enzymes using 221 naturally occurring prenylated flavonoids, followed by molecular dynamics simulation (100 ns), density functional theory (B3LYP model), and ADMET (admeSar 2 online server) studies. The result obtained from the virtual screening with the glucokinase revealed arcommunol B (−10.1 kcal/mol), kuwanon S (−9.6 kcal/mol), manuifolin H (−9.5 kcal/mol), and kuwanon F (−9.4 kcal/mol) as the top-ranked molecules. Additionally, the molecular dynamics simulation and MM/GBSA calculations showed that the hit molecules were stable at the active site of the glucokinase enzyme. Furthermore, the DFT and ADMET studies revealed the hit molecules as potential glucokinase activators and drug-like candidates. Our findings suggested further evaluation of the top-ranked prenylated flavonoids for their in vitro and in vivo glucokinase activating potentials.

We investigated the effects of the prenylated flavonoid-standardized extract (PFE) from the seeds of Psoralea corylifolia L. on countering obesity, which increases energy expenditure and stimulates thermogenesis in subcutaneous white adipose tissue (sWAT) and brown adipose tissue (BAT). For 12 weeks, C57BL/6 mice were fed a controlled high-fat diet (HFD) or HFDs with 0.2% or 0.5% w/w PFE. In vitro, the differentiation of 3 T3-L1 cells was used to elicit thermogenesis in the presence of PFE. PFE obviously reduced body weight and fat mass in a dose-dependent manner, increased energy expenditure, improved insulin sensitivity, and prevented hepatic steatosis by increasing lipid oxidation and secretion in HFD-fed mice. Moreover, PFE induced clear browning in sWAT, significantly increased phosphorylation of AMPKα1/2 and p38, increased BAT activity and the differentiation of 3 T3-L1 by increasing the expression of uncoupling protein 1 and other thermogenic genes. Our study showed that PFE prevented obesity by increasing browning and activating thermogenic genes in sWAT and BAT, improving glucose homeostasis, and protecting hepatic steatosis. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A new alopecurone structure (alopecurone P) with three known compounds were isolated from the roots of Sophora pachycarpa. • The absolute configuration of alopecurones J and P were characterized by ECD method using time dependent density function theory (TDDFT). • Alopecurone J and P showed cytotoxic effect on MCF-7 cell line through Wnt signaling pathway. Abstract A new prenylated flavonostilbene, namely, alopecurone P together with three known compounds sophoraflavanone G, 2-(4-hydroxyphenyl)-2,3-dihydrobenzo[ b ]furan-3,4,6-triol and alopecurone J were characterized from the roots of Sophora pachycarpa. The absolute configuration of alopecurones J and P were characterized by comparison of experimental electronic circular dichroism (ECD) spectroscopy and simulated data using time-dependent density functional theory (TDDFT) for possible stereoisomers. The cytotoxic properties of isolated compounds have also been evaluated on two breast cancer cell lines (MCF-7 and MDA-MB-231) and normal cell line (NIH/3T3) using AlamarBlue®, flowcytometry and western blot assays. Alopecurone J and P showed cytotoxic effect on MCF-7 cell line through Wnt signaling pathway. It seems that the presence of lavandulyl substitution in C-8 position of flavanone structure increased the cytotoxic effect. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • In vitro antiplasmodial activity of prenylated flavonoids from Erythrina latissima. • Moderate antiplasmodial activities, mostly accompanied by cytotoxicity. • Prenylated flavonoids are a promising scaffold for antiplasmodial compounds. Abstract The antiplasmodial activity against Plasmodium falciparum strain K1 as well as cytotoxicity against MRC-5 cells of 15 prenylated flavonoids obtained from Erythrina latissima E. Mey (Leguminosae) from South Africa was determined. Although initially some promising activities were observed, with 5′-prenyl-pratensein being the most selective compound, most IC 50 values varied from 1 to 30 μM, with cytotoxicities in the same range, resulting in selectivity indices <10. The prenylated flavonoid scaffold can be considered as a promising skeleton for antiplasmodial compounds, but structural modifications to reduce the cytotoxiciy and to improve the selectivity will be necessary. [ABSTRACT FROM AUTHOR]

The genus Sophora (Fabaceae) has been used in traditional medicine for years. Prenylated flavonoids are one of the constituents of Sophora species that play important roles in their biological properties. Different classes of prenylated flavonoids are produced by Sophora spp. including prenylated flavonol (e.g., sophoflavescenol), prenylated flavanone (e.g., sophoraflavanone G), prenylated flavonostilbene (e.g., alopecurones A and B), and prenylated chalcone (kuraridin). Prenylated flavonoids have a more lipophilic structure, which leads to its high affinity to the cell membranes and enhancement of the biological activity, which includes cytotoxicity, antibacterial, anti-inflammatory, and estrogenic activities. However, it is reported that prenylation decreases the plasma absorption but increases the tissue accumulation. The presence of the prenyl or lavandulyl groups on C8 position of flavonoids plays an important role in the biological activity. It seems that prenylated flavonoids have the potential to be developed as new drugs or supplements for human health. [ABSTRACT FROM AUTHOR]

We have used an original technology (Plant Milking Technology) based on aeroponic cultivation of plants associated with the gentle recovery of active ingredients from roots. Extraction of bioactive molecules was achieved by soaking the roots, still attached to the living plants, into a nontoxic solvent for a 2 h period. This nondestructive recovery process allows using the same root biomass for successive harvesting dates, in a recyclable way. We have applied this technology to Morus alba L. (mulberry tree), an emblematic tree of the Traditional Chinese Medicine (TCM). Trees were aeroponically grown in large-scale devices (100 m2) and were submitted to nitrogen deprivation to increase the content in active molecules (prenylated flavonoids). The Plant Milking technology applied to Morus alba L. allowed to produce an extract enriched in prenylated compounds (18-fold increase when compared to commercial root extract). Prenylated flavonoids (moracenin A and B, kuwanon C, wittiorumin F, morusin) presented a high affinity for the aged-associated collagenase enzyme, which was confirmed by activity inhibition. In accordance, M. alba extract presents efficient properties to regulate the skin matrisome, which is critical during skin aging. The benefits have been especially confirmed in vivo on wrinkle reduction, in a clinical study that involved aged women. Plant Milking technology is an optimal solution to produce active ingredients from plant roots, including trees, that meet both customer expectations around sustainability, as well as the need for an efficient production system for biotechnologists.

Beer is a fermented beverage with beneficial phenolic compounds and is widely consumed worldwide. The current study aimed to describe the content of three families of phenolic compounds with relevant biological activities: prenylated flavonoids (from hops), simple phenolic alcohols (from fermentation) and alkylresorcinols (from cereals) in a large sample of beers (n = 45). The prenylated flavonoids analyzed were xanthohumol, isoxanthohumol, 6- and 8-prenylnaringenin. The total prenylated flavonoids present in beer ranged from 0.0 to 9.5 mg/L. The simple phenolic alcohols analyzed were tyrosol and hydroxytyrosol, ranging from 0.2 to 44.4 and 0.0 to 0.1 mg/L, respectively. Our study describes, for the first time, the presence of low amounts of alkylresorcinols in beer, in concentrations ranging from 0.02 to 11.0 µg/L. The results in non-alcoholic beer and the differences observed in the phenolic composition among different beer types and styles highlight the importance of the starting materials and the brewing process (especially fermentation) on the final phenolic composition of beer. In conclusion, beer represents a source of phenolic compounds in the diet that could act synergistically, triggering beneficial health effects in the context of its moderate consumption.

Pterocaulon genus comprises 26 species, half of them have been phytochemical investigations regarding the chemical composition, and coumarins have been considered the chemotaxonomic markers in the genus. Herein Pterocaulon angustifolium DC (Asteraceae), a native plant from Brazil, is investigated for the first time. Twenty-six compounds were isolated from aerial parts of P. angustifolium DC., being 5 triterpenes, 4 phytosterols, 9 flavonoids, 3 phenolic acids, and 5 coumarins. Moreover, a total of 177 compounds were putatively identified using the dereplication technique by UHPLC-HRMS/MS, more than 50% correspond to flavonoids and coumarins. Although 41 different coumarins have already been reported in Pterocaulon genus, 16 were identified for the first time in this study. Crude ethanolic extract and fractions of P. angustifolium were also biologically investigates, and dichloromethane fraction was the most active fraction in the evaluation of antiproliferative, antioxidant, antimicrobial and cholinesterase inhibitory activities.

The influence of a prenylated flavonoid-6-prenylnaringenin (6-PR) and selected non-prenylated flavonoids: acacetin, chrysin, baicalein, wogonin, and luteolin on the activity of voltage-gated potassium channels Kv1.3 was investigated in human leukemic Jurkat T cells. Electrophysiological measurements were accompanied by studies on the cytotoxic effect of the examined compounds on Jurkat T cells. Electrophysiological studies were performed using the whole-cell patch-clamp technique. Cell viability was determined using the MTT assay. 6-PR inhibited Kv1.3 channels in Jurkat T cells in a concentration-dependent manner. The estimated value of the half-blocking concentration (EC50) was about 5.76 µM. Among non-prenylated flavonoids, acacetin and chrysin inhibited Kv1.3 channels in Jurkat T cells when applied at the concentration of 30 µM, whereas baicalein, wogonin, and luteolin were ineffective at this concentration. The inhibitory effects of acacetin and chrysin on Kv1.3 channels were significantly less potent than the inhibition caused by 6-PR. All tested compounds inhibited growth of Jurkat T cells in a concentration-dependent manner. Wogonin and chrysin were the most cytotoxic flavonoids tested, whereas baicalein and 6-PR were the least cytotoxic compounds. In accordance to our hypothesis the prenylated flavonoid (6-PR) was much more effective inhibitor of Kv1.3 channels than non-prenylated compounds selected for this study. The inhibition of Kv1.3 channels by 6-PR, acacetin, and chrysin was not related to cytotoxicity of these compounds. The channels' inhibition might be involved in anti-proliferative and pro-apoptotic effects of 6-PR, acacetin and chrysin observed in cancer cell lines expressing these channels. [ABSTRACT FROM AUTHOR]