An activity-guided isolation study on the EtOH extract prepared from the bulbs of Prospero autumnale yielded four new phenolic compounds, including a new stilbenoid (1), a new homoisoflavonoid derivative (8), a new homoisoflavonoid dimer (9), and an unprecedented homoisoflavone-stilbene heterodimer (10), together with six known (2-7) analogs. Their chemical structures were elucidated by spectroscopic analysis and theoretical NMR and ECD calculations. Compounds 9 and 10 are unique in their scaffolds. The in vitro cytotoxic activity of purified compounds was evaluated against eight tumor cell lines (HCT116, LoVo, DU145, PC3, HEP3B, HEPG2, MCF7, and MDA-MB-231) and one nontumor cell line (L929) by the MTS assay. Compounds 1, 2, 4, and 10 exhibited inhibition with IC50 values ranging from 8.2 to 37.6 μM. Cytotoxic cell death mechanisms were further investigated, indicating variability in apoptosis, necrosis, or cell cycle arrest.
- MeSH
- antitumorózní látky fytogenní * farmakologie chemie MeSH
- apoptóza účinky léků MeSH
- isoflavony farmakologie chemie izolace a purifikace MeSH
- kořeny rostlin chemie MeSH
- léky antitumorózní - screeningové testy MeSH
- lidé MeSH
- molekulární struktura MeSH
- nádorové buněčné linie MeSH
- stilbeny * farmakologie chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antitumorózní látky fytogenní * MeSH
- isoflavony MeSH
- stilbeny * MeSH
Heteroleptic copper(II) complexes, containing prenylated flavonoid osajin isolated from the fruits of Maclura pomifera Schneid., were prepared and thoroughly characterized, including single crystal X-ray analysis. Some of the following complexes of the general composition [Cu(L)(bpy)]NO3 (1), [Cu(L)(dimebpy)]NO3·2MeOH (2) [Cu(L)(phen)]NO3·H2O (3), [Cu(L)(bphen)]NO3 (4) and [Cu(L)(dppz)]NO3 (5), where HL stands for 3-(4-hydroxyphenyl)-5-hydroxy-8,8-dimethyl-6-(3-methylbut-2-ene-1-yl)-4H,8H-benzo[1,2-b:3,4-b']dipyran-4-one (osajin), 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, were also monitored for their solution stability and interactions with cysteine and glutathione by mass spectrometry. The in vitro cytotoxicity of the complexes was evaluated against a panel of eight human cancer cell lines: (MCF-7, HOS, A549, PC-3, A2780, A2780R, Caco-2, and THP-1). The results revealed high antiproliferative activity of the complexes with the best IC50 values of 0.5-3.4 μM for complexes (4) and (5), containing the bulkier N,N'-donor ligands (bphen, and dppz, respectively). The complexes also revealed a relatively low toxicity towards human hepatocytes (IC50 values are higher than 100 μM in some cases), and thus proved to be highly selective towards the cancer cells. On the other hand, the complexes showed a strong in vitro nuclease effect using the model pUC-19 plasmid. In the model of lipopolysaccharide-stimulated (LPS) THP-1 monocytes, the complexes revealed ability to lower the activity of nuclear factor kappa-B/activator protein 1 (NF-κB /AP-1) system and decrease the secretion of tumor necrosis factor alpha (TNF-α). Thus, the complexes have been identified as strong antiproliferative and anti-inflammatory compounds.
- Klíčová slova
- Cell viability, Copper(II) complexes, In vitro cytotoxicity, Inflammation, Osajin, X-ray structure,
- MeSH
- antiflogistika * chemie farmakologie MeSH
- buňky A549 MeSH
- buňky PC-3 MeSH
- Caco-2 buňky MeSH
- hepatocyty metabolismus MeSH
- isoflavony * chemie farmakologie MeSH
- komplexní sloučeniny * chemie farmakologie MeSH
- lidé MeSH
- měď * chemie farmakologie MeSH
- MFC-7 buňky MeSH
- proliferace buněk účinky léků MeSH
- THP-1 buňky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antiflogistika * MeSH
- isoflavony * MeSH
- komplexní sloučeniny * MeSH
- měď * MeSH
- osajin MeSH Prohlížeč
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.
- Klíčová slova
- ROS, cell cycle, copper(II) complexes, in vitro cytotoxicity, inflammation, nuclease activity, pomiferin,
- 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
- Názvy látek
- antiflogistika MeSH
- antitumorózní látky MeSH
- benzopyrany MeSH
- flavonoidy MeSH
- isoflavony MeSH
- komplexní sloučeniny MeSH
- měď MeSH
- pomiferin MeSH Prohlížeč
- reaktivní formy kyslíku 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.
- Klíčová slova
- OECD test guidelines, Renilla luciferase, alternative methods, firefly luciferase, inhibition, isoflavonoids, molecular docking, quantitative structure–activity relationships, reporter-gene assay,
- 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
- Názvy látek
- isoflavony MeSH
- luciferasy renil 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.
- Klíčová slova
- biochanin A, daidzein, equol, formononetin, genistein, glycitein, isoflavones, phytoestrogens,
- 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
- Názvy látek
- biochanin A MeSH Prohlížeč
- daidzein MeSH Prohlížeč
- equol MeSH
- formononetin MeSH Prohlížeč
- fytoestrogeny MeSH
- genistein MeSH
- glycitein MeSH Prohlížeč
- isoflavony 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.
- Klíčová slova
- Dyer’s Greenweed, elicitation, heavy metals, plasma membrane transport,
- MeSH
- buněčné kultury metody MeSH
- Genista chemie cytologie účinky léků MeSH
- isoflavony chemie MeSH
- sekundární metabolismus účinky léků MeSH
- sloučeniny vanadu farmakologie MeSH
- vanadáty farmakologie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ammonium metavanadate MeSH Prohlížeč
- isoflavony MeSH
- sloučeniny vanadu MeSH
- vanadáty MeSH
- vanadyl sulfate MeSH Prohlížeč
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.
- Klíčová slova
- angiogenesis, breast cancer, galectins, genistein, soy,
- 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
- Názvy látek
- genistein MeSH
- inhibitory angiogeneze MeSH
- isoflavony MeSH
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.
- Klíčová slova
- antimicrobial activity, demethyltexasin, isoflavonoids, methicillin-resistant Staphylococcus aureus, minimum inhibitory concentration,
- 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
- Názvy látek
- 6,7,4'-trihydroxyisoflavone MeSH Prohlížeč
- 7,8,4'-trihydroxyisoflavone MeSH Prohlížeč
- antibakteriální látky MeSH
- biochanin A MeSH Prohlížeč
- daidzein MeSH Prohlížeč
- genistein MeSH
- isoflavony MeSH
- methicilin MeSH
- rostlinné extrakty 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.
- Klíčová slova
- Genista tinctoria L, electric current, isoflavonoids, silver nitrate,
- MeSH
- buněčné kultury MeSH
- dusičnan stříbrný MeSH
- elektřina MeSH
- fyziologický stres * MeSH
- Genista chemie MeSH
- isoflavony analýza biosyntéza chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- daidzein MeSH Prohlížeč
- dusičnan stříbrný MeSH
- genistin MeSH Prohlížeč
- isoflavony 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.
- Klíčová slova
- Amaryllidaceae, ELISA, HPLC-ESI-MS, immunoaffinity chromatography, isoflavonoid,
- 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
- Názvy látek
- alkaloidy MeSH
- biochanin A MeSH Prohlížeč
- daidzein MeSH Prohlížeč
- genistein MeSH
- isoflavony MeSH
