A series of new heteroleptic copper(II) complexes of the composition [Cu(L)(bpy)]NO3·2MeOH (1), [Cu(L)(dimebpy)]NO3·2H2O (2), [Cu(L)(phen)]NO3·2MeOH (3), [Cu(L)(bphen)]NO3·MeOH (4), [Cu(L)(dppz)]NO3·MeOH (5) was prepared, where HL = 3-(3,4-dihydroxyphenyl)-5-hydroxy-8,8-dimethyl-6-(3-methylbut-2-ene-1-yl)-4H,8H-benzo[1,2-b:3,4-b']dipyran-4-one, (pomiferin) and bpy = 2,2'-bipyridine, dimebpy = 4,4'-dimethyl-2,2'-bipyridine, phen = 1,10-phenanthroline, bphen = 4,7-diphenyl-1,10-phenanthroline, and dppz = dipyrido[3,2-a:2',3'-c]phenazine. The complexes were characterized using elemental analysis, infrared and UV/Vis spectroscopies, mass spectrometry, thermal analysis and conductivity measurements. The in vitro cytotoxicity, screened against eight human cancer cell lines (breast adenocarcinoma (MCF-7), osteosarcoma (HOS), lung adenocarcinoma (A549), prostate adenocarcinoma (PC-3), ovarian carcinoma (A2780), cisplatin-resistant ovarian carcinoma (A2780R), colorectal adenocarcinoma (Caco-2) and monocytic leukemia (THP-1), revealed the complexes as effective antiproliferative agents, with the IC50 values of 2.2-13.0 μM for the best performing complexes 3 and 5. All the complexes 1-5 showed the best activity against the A2780R cells (IC50 = 2.2-6.6 μM), and moreover, the complexes demonstrated relatively low toxicity on healthy human hepatocytes, with IC50 > 100 μM. The complexes were evaluated by the Annexin V/propidium iodide apoptosis assay, induction of cell cycle modifications in A2780 cells, production of reactive oxygen species (ROS), perturbation of mitochondrial membrane potential, inhibition of apoptosis and inflammation-related signaling pathways (NF-κB/AP-1 activity, NF-κB translocation, TNF-α secretion), and tested for nuclease mimicking activity. The obtained results revealed the corresponding complexes to be effective antiproliferative and anti-inflammatory agents.
- MeSH
- antiflogistika farmakologie MeSH
- antitumorózní látky farmakologie MeSH
- apoptóza účinky léků MeSH
- benzopyrany chemie farmakologie MeSH
- flavonoidy metabolismus farmakologie MeSH
- isoflavony chemie farmakologie MeSH
- komplexní sloučeniny chemie farmakologie MeSH
- lidé MeSH
- měď chemie metabolismus farmakologie MeSH
- nádorové buněčné linie MeSH
- proliferace buněk účinky léků MeSH
- reaktivní formy kyslíku metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Firefly luciferase is susceptible to inhibition and stabilization by compounds under investigation for biological activity and toxicity. This can lead to false-positive results in in vitro cell-based assays. However, firefly luciferase remains one of the most commonly used reporter genes. Here, we evaluated isoflavonoids for inhibition of firefly luciferase. These natural compounds are often studied using luciferase reporter-gene assays. We used a quantitative structure-activity relationship (QSAR) model to compare the results of in silico predictions with a newly developed in vitro assay that enables concomitant detection of inhibition of firefly and Renilla luciferases. The QSAR model predicted a moderate to high likelihood of firefly luciferase inhibition for all of the 11 isoflavonoids investigated, and the in vitro assays confirmed this for seven of them: daidzein, genistein, glycitein, prunetin, biochanin A, calycosin, and formononetin. In contrast, none of the 11 isoflavonoids inhibited Renilla luciferase. Molecular docking calculations indicated that isoflavonoids interact favorably with the D-luciferin binding pocket of firefly luciferase. These data demonstrate the importance of reporter-enzyme inhibition when studying the effects of such compounds and suggest that this in vitro assay can be used to exclude false-positives due to firefly or Renilla luciferase inhibition, and to thus define the most appropriate reporter gene.
- MeSH
- isoflavony chemie metabolismus MeSH
- luciferasy renil chemie metabolismus MeSH
- reportérové geny genetika fyziologie MeSH
- sekundární struktura proteinů MeSH
- světluškovití MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Phytoestrogens are naturally occurring nonsteroidal phenolic plant compounds that, due to their molecular structure and size, resemble vertebrate steroids estrogens. This review is focused on plant flavonoids isoflavones, which are ranked among the most estrogenic compounds. The main dietary sources of isoflavones for humans are soybean and soybean products, which contain mainly daidzein and genistein. When they are consumed, they exert estrogenic and/or antiestrogenic effects. Isoflavones are considered chemoprotective and can be used as an alternative therapy for a wide range of hormonal disorders, including several cancer types, namely breast cancer and prostate cancer, cardiovascular diseases, osteoporosis, or menopausal symptoms. On the other hand, isoflavones may also be considered endocrine disruptors with possible negative influences on the state of health in a certain part of the population or on the environment. This review deals with isoflavone classification, structure, and occurrence, with their metabolism, biological, and health effects in humans and animals, and with their utilization and potential risks.
- MeSH
- equol chemie klasifikace metabolismus MeSH
- fytoestrogeny chemie klasifikace metabolismus MeSH
- genistein chemie klasifikace metabolismus MeSH
- isoflavony chemie klasifikace metabolismus MeSH
- lidé MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The family Fabaceae traditionally serves as a food and herbal remedies source. Certain plants serve for treatment of menopausal symptoms based on a presence of typical secondary metabolites, isoflavones. Beside soybean and clovers, other plants or cultures in vitro can produce these molecules. A cultivation in vitro can be enhanced by elicitation that stimulates metabolites biosynthesis via stress reaction. Vanadium compounds have been already described as potential elicitors, and the aim of this study was to determine the impact of NH₄VO₃ and VOSO₄ solutions on isoflavones production in Genista tinctoria L. cell cultures. The significant increase of isoflavones content, such as genistin, genistein, or formononetin, was measured in a nutrient medium or dry mass after NH₄VO₃ treatment for 24 or 48 h. The possible transport mechanism of isoflavones release as a result of elicitation was further evaluated. An incubation with different transport inhibitors prior to elicitation took effect on isoflavones content in the medium. However, there was a non-ended result for particular metabolites such as genistein and daidzein, where ATP-binding cassette (ABC) or, alternatively, multidrug and toxin extrusion (MATE) proteins can participate. Possible elicitation by some inhibitors was discussed as a result of their pleiotropic effect. Despite this outcome, the determination of the transport mechanism is an important step for identification of the specific transporter.
UNLABELLED: In this study, we tested 15 naturally occurring isoflavones and their metabolites for their possible antibacterial properties against nine Gram-positive and Gram-negative bacteria. The in vitro antibacterial activity was determined using the broth microdilution method, and the results were expressed as minimum inhibitory concentrations (MICs). 6,7,4'-trihydroxyisoflavone (demethyltexasin), 7,3',4'-trihydroxyisoflavone (hydroxydaidzein), 5,7-dihydroxy-4'-methoxyisoflavone (biochanin A), 7,8,4'-trihydroxyisoflavone (demethylretusin) and 5,7,4'-trihydroxyisoflavone (genistein) produced significant antibacterial activity (MICs ≥ 16 μg ml(-1)). The most effective compound, demethyltexasin, was subsequently tested for its growth-inhibitory effect against Staphylococcus aureus, and it exhibited significant antistaphylococcal effects against various standard strains and clinical isolates, including methicillin and tetracycline resistant ones with the MICs ranging from 16 to 128 μg ml(-1). SIGNIFICANCE AND IMPACT OF THE STUDY: The results of the structure-activity relationship (SAR) analysis identified ortho-dihydroxyisoflavones as a class of antibacterially effective compounds emphasizing the hydroxyl groups at C-5, 6 and 7 positions as crucial supposition for the antibacterial action of plant isoflavones and their metabolites. Demethyltexasin, an isoflavones' metabolite present in the human body through enterohepatic recycling of soya bean isoflavones (daidzein, genistein), showed the most potent antibacterial activity, especially against various strains of Staphylococcus aureus (including MDR and MRSA). The significance of this study is a deepening of the knowledge on isoflavones' SAR and identification of the antistaphylococcal activity of demethyltexasin, which suggest that metabolites of isoflavones can be even more potent antibacterial agents than their precursors.
- MeSH
- antibakteriální látky chemie farmakologie MeSH
- genistein farmakologie MeSH
- gramnegativní bakterie účinky léků MeSH
- isoflavony chemie farmakologie MeSH
- lidé MeSH
- methicilin farmakologie MeSH
- mikrobiální testy citlivosti MeSH
- rostlinné extrakty farmakologie MeSH
- Staphylococcus aureus účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Epidemiological studies have revealed that high consumption of soy products is associated with low incidences of hormone-dependent cancers, including breast and prostate cancer. Soybeans contain large amounts of isoflavones, such as the genistein and daidzain. Previously, it has been demonstrated that genistein, one of the predominant soy isoflavones, can inhibit several steps involved in carcinogenesis. It is suggested that genistein possesses pleiotropic molecular mechanisms of action including inhibition of tyrosine kinases, DNA topoisomerase II, 5α-reductase, galectin-induced G2/M arrest, protein histidine kinase, and cyclin-dependent kinases, modulation of different signaling pathways associated with the growth of cancer cells (e.g., NF-κB, Akt, MAPK), etc. Moreover, genistein is also a potent inhibitor of angiogenesis. Uncontrolled angiogenesis is considered as a key step in cancer growth, invasion, and metastasis. Genistein was found to inhibit angiogenesis through regulation of multiple pathways, such as regulation of VEGF, MMPs, EGFR expressions and NF-κB, PI3-K/Akt, ERK1/2 signaling pathways, thereby causing strong antiangiogenic effects. This review focuses on the antiangiogenic properties of soy isoflavonoids and examines their possible underlying mechanisms.
- MeSH
- genistein chemie farmakologie terapeutické užití MeSH
- Glycine max chemie MeSH
- inhibitory angiogeneze chemie farmakologie terapeutické užití MeSH
- isoflavony chemie farmakologie terapeutické užití MeSH
- lidé MeSH
- nádory prsu krevní zásobení farmakoterapie metabolismus patologie MeSH
- patologická angiogeneze farmakoterapie metabolismus patologie MeSH
- prsy krevní zásobení účinky léků metabolismus patologie MeSH
- signální transdukce účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
The increased content of isoflavonoids in dry cell suspension and nutrient medium was observed after application of electric current and AgNO3 on Genista tinctoria L. cultures in vitro. The highest content of genistin (1.7 mg g(- 1) DW - dry weight) was measured in the dry cell suspension culture after 30 min elicitation of 10 V and 6 h cultivation and daidzein content (3.5 mg g(- 1) DW) was measured after 60 min elicitation of 5 V and 24 h cultivation. In the case of AgNO3 elicitation, the content of genistin in dry cell suspension culture (0.5 mg g(- 1) DW) was highest after 48 h of AgNO3 treatment and concentration of 5.9 × 10(- 4) mol/L. The AgNO3 concentration of 5.9 × 10(- 4) mol/L was also the most effective combination for daidzein production (0.9 mg g(- 1) DW) after 168 h. The results of this study show that the secondary metabolites could also be released from G. tinctoria L. cells into the nutrient medium.
Byl sledován vliv exogenní aplikace kyseliny jasmonové (JA) v kombinaci s vápníkem a verapamilem (blokátor vápníkového kanálu) na produkci flavonoidů a isoflavonoidů suspenzní kulturou Trifolium pratense L. Kultura byla kultivována při teplotě 25 °C a světelné periodě 16 hodin světlo/8 hodin tma na živném médiu podle Gamborga s přídavkem 2 mg.l-1 2,4-dichlorfenoxyoctové kyseliny a 2 mg.l-1 6-benzylaminopurinu. Nejlepší vliv kyseliny jasmonové na produkci flavonoidů a isoflavonoidů se projevil po 24hodinové aplikaci koncentrace 50 μmol.l-1. Maximální produkce elicitované suspenzní kultury byla zjištěna, když buňky byly ošetřeny vysokou dávkou vápníku (10 mmol.l-1). Přidání všech koncentrací verapamilu k suspenzní kultuře elicitované JA snížilo produkci flavonoidů a isoflavonoidů.
Effect of exogenously applied jasmonic acid (JA) in combination with calcium and verapamil (a calcium channels blocker) on the production of flavonoids and isoflavonoids in suspension cultures of Trifolium pratense L. was investigated. The culture was cultivated in Gamborg medium with an addition of 2 mg.l-1 of 2,4-dichlorophenoxyacetic acid and 2 mg.l-1 of 6-benzylaminopurine, at the temperature of 25 °C, 16-hr light/8-hr dark period. The best effect of jasmonic acid on the production of flavonoids and isoflavonoids was manifested after a 24-hour application of the 50 μmol.l-1 concentration. The maximum production of JA-induced suspension culture was observed when cells were treated with a high level of calcium (10 mmol.l-1). The addition of all concentrations of verapamil to JA-induced suspension culture decreased production of flavonoids and isoflavonoids.
- MeSH
- 2-aminopurin analogy a deriváty chemie MeSH
- buněčné kultury metody přístrojové vybavení MeSH
- farmaceutická technologie MeSH
- flavonoidy * chemie izolace a purifikace MeSH
- fytoestrogeny * chemie izolace a purifikace MeSH
- isoflavony * chemie izolace a purifikace MeSH
- kultivační média MeSH
- kultivační techniky metody přístrojové vybavení využití MeSH
- kyselina 2,4-dichlorfenoxyoctová chemie MeSH
- kyselina alfa-linolenová analogy a deriváty chemie MeSH
- modulátory membránového transportu MeSH
- proteinkinasy závislé na vápníku a kalmodulinu chemie MeSH
- regulátory růstu rostlin chemie MeSH
- rostlinné extrakty chemie izolace a purifikace MeSH
- spektrofotometrie metody využití MeSH
- Trifolium * chemie MeSH
- vápník chemie MeSH
- vápníkové kanály chemie MeSH
- verapamil chemie MeSH
- Publikační typ
- práce podpořená grantem MeSH
Plants of the Amaryllidaceae family are known as producers of biologically active alkaloids. Besides these a variety of flavonoids, including flavones, chalcones and chromones, have been detected in the Amaryllidaceous plants. In this study, we have analysed 16 representatives of the family for the presence of isoflavonoids. The water/ethanolic extracts were analysed with HPLC-ESI-MS both without any pre-treatment and after immunoaffinity chromatography as a clean-up step. Four individual immunosorbents specific for biochanin A, daidzein and genistein were used. In addition, five enzyme-linked immunosorbent assays specific for the above-mentioned isoflavonoids and their derivatives have been used for the analysis of the extracts after fractionation by semi-preparative HPLC. Fifteen selected isoflavonoids were detected in the studied samples, and the amount of individual compounds ranged between ca. 0.8 and 400 ng/g of dry weight. This study extends the number of known isoflavonoid-producing families within the monocotyledonous plants.
- MeSH
- alkaloidy chemie izolace a purifikace farmakologie MeSH
- elektronová paramagnetická rezonance MeSH
- ELISA MeSH
- genistein izolace a purifikace MeSH
- isoflavony chemie izolace a purifikace farmakologie MeSH
- liliovité chemie MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Fytoestrogeny představují různorodou skupinu rostlinných látek většinou fenylpropanového metabolizmu, které napodobují svou strukturou živočišné estrogeny a mají různé úrovně estrogenní aktivity. Nejaktivnější fytoestrogeny jsou izoflavony, zejména daidzein a genistein. Také izoflavony z jetele lučního (Trifolium pratense L., Fabaceae) zmírňují menopauzální symptomy a mají význam při prevenci osteoporózy, nádorových a kardiovaskulárních onemocnění.
Phytoestrogens are a diverse group of plant substances, mostly phenylpropanoid metabolism, which imitate the structure of animal estrogens and have different levels of estrogenic activity. The most active phytoestrogens are the isoflavones daidzein and genistein, especially. Also the isoflavones from red clover (Trifolium pratense L., Fabaceae) reduce menopausal symptoms and are relevant in the prevention of osteoporosis, cancer and cardiovascular disease.
- Klíčová slova
- daidzein,
- MeSH
- Fabaceae MeSH
- fytoestrogeny farmakologie MeSH
- genistein farmakologie chemie terapeutické užití MeSH
- isoflavony * farmakologie chemie terapeutické užití MeSH
- lidé MeSH
- menopauza * účinky léků MeSH
- nápoje MeSH
- postmenopauzální osteoporóza prevence a kontrola MeSH
- potravní doplňky MeSH
- Trifolium * chemie MeSH
- Check Tag
- lidé MeSH
