scholarly journals Binding of Red Clover Isoflavones to Actin as A Potential Mechanism of Anti-Metastatic Activity Restricting the Migration of Cancer Cells

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2471 ◽  
Author(s):  
Grażyna Budryn ◽  
Joanna Grzelczyk ◽  
Horacio Pérez-Sánchez
Keyword(s):  
Therapeutic Potential ◽  
Docking Simulation ◽  
Red Clover ◽  
Biochanin A ◽  
Titration Calorimetry ◽  
Atp Binding Site ◽  
Cytoskeleton Reorganization ◽  
Metastatic Activity ◽  
Derivatives Of ◽  
Formation Of Complexes

Actin functions are crucial for the ability of the cell to execute dynamic cytoskeleton reorganization and movement. Nutraceuticals that form complexes with actin and reduce its polymerization can be used in cancer therapy to prevent cell migration and metastasis of tumors. The aim of this study was to evaluate the ability of isoflavones to form complexes with actin. Docking simulation and isothermal titration calorimetry were used for this purpose. The formation of complexes by hydrogen bonds, hydrophobic and π-π interactions was demonstrated. Interactions occurred at the ATP binding site, which may limit the rotation of the actin molecule observed during polymerization and also at the site responsible for contacts during polymerization, reducing the ability of the molecule to form filaments. The greatest therapeutic potential was demonstrated by isoflavones occurring in red clover sprouts, i.e., biochanin A and formononetin, being methoxy derivatives of genistein and daidzein.

The acylated isoflavone glycosides from subterranean clover and red clover

1971 ◽  
Vol 24 (7) ◽  
pp. 1509 ◽  
Author(s):  
AB Beck ◽  
JR Knox
Keyword(s):  
Methyl Esters ◽  
Red Clover ◽  
Subterranean Clover ◽  
Pure Form ◽  
Biochanin A ◽  
Structural Assignment ◽  
Derivatives Of

Formononetin and biochanin A 7-O-glucosides (1a and 2a) and their malonate hemi-ester derivatives (1b and 2b) have been isolated from red clover and from the Yarloop strain of subterranean clover. Structure (2b) is a correction of an earlier structural assignment to this compound. Small amounts of the derived methyl esters (1c and 2c) are also present in both clovers. Similar derivatives of genistein have been obtained from the Yarloop strain, although only the 7-O-glucoside (3a) has been isolated in pure form. Studies on red clover and on nine strains of subterranean clover have demonstrated in all cases that the acidic malonate esters account for the predominant proportion of the glycosides.

Therapeutic Potential of Biochanin-A Against Isoproterenol-Induced Myocardial Infarction in Rats

2020 ◽  
Vol 18 (1) ◽  
pp. 31-36 ◽  
Author(s):  
Sangeethadevi Govindasami ◽  
Veera Venkata Sathibabu Uddandrao ◽  
Nivedha Raveendran ◽  
Vadivukkarasi Sasikumar
Keyword(s):  
Myocardial Infarction ◽  
Antioxidant Enzymes ◽  
Therapeutic Potential ◽  
Biochanin A ◽  
Glutathione S Transferase ◽  
Serum Glutamic Oxaloacetic Transaminase ◽  
Creatine Kinase Mb ◽  
Male Wistar Rats ◽  
Detoxifying Enzyme ◽  
Cardioprotective Effects

Background: This study determined the effect of Biochanin A (BCA) on isoproterenol (ISO) induced Myocardial Infarction (MI) in male Wistar rats. Methods: Animals (weighing 150-180 g) were divided into four groups, with six animals in each group and pretreated with BCA (10mg/kg Body Weight [BW]) and ɑ-tocopherol (60mg/kg BW) for 30 days; and ISO (20mg/kg BW) was administrated subcutaneously on the 31st and 32nd day. Results: ISO-induced MI rats demonstrated the significant elevation of serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, lactate dehydrogenase, creatine kinase-MB and cardiac troponin; however, concomitant pretreatment with BCA protected the rats from cardiotoxicity caused by ISO. Activities of antioxidant enzymes, such as superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase significantly reduced in the heart with ISO-induced MI. Pretreatment with BCA produced a marked reversal of these antioxidant enzymes related to MI-induced by ISO. Conclusion: In conclusion, this study suggested that BCA exerts cardioprotective effects through modulating lipid peroxidation, enhancing antioxidants, and detoxifying enzyme systems.

scholarly journals Crizotinib acts as ABL1 inhibitor combining ATP-binding with allosteric inhibition and is active against native BCR-ABL1 and its resistance and compound mutants BCR-ABL1T315I and BCR-ABL1T315I-E255K

2021 ◽  
Author(s):  
Afsar Ali Mian ◽  
Isabella Haberbosch ◽  
Hazem Khamaisie ◽  
Abed Agbarya ◽  
Larissa Pietsch ◽  
...  
Keyword(s):  
Binding Site ◽  
Kinase Inhibitors ◽  
Therapeutic Potential ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Binding Pocket ◽  
Atp Binding ◽  
Atp Binding Site ◽  
Lung Cancer Patients

AbstractResistance remains the major clinical challenge for the therapy of Philadelphia chromosome–positive (Ph+) leukemia. With the exception of ponatinib, all approved tyrosine kinase inhibitors (TKIs) are unable to inhibit the common “gatekeeper” mutation T315I. Here we investigated the therapeutic potential of crizotinib, a TKI approved for targeting ALK and ROS1 in non-small cell lung cancer patients, which inhibited also the ABL1 kinase in cell-free systems, for the treatment of advanced and therapy-resistant Ph+ leukemia. By inhibiting the BCR-ABL1 kinase, crizotinib efficiently suppressed growth of Ph+ cells without affecting growth of Ph− cells. It was also active in Ph+ patient-derived long-term cultures (PD-LTCs) independently of the responsiveness/resistance to other TKIs. The efficacy of crizotinib was confirmed in vivo in syngeneic mouse models of BCR-ABL1- or BCR-ABL1T315I-driven chronic myeloid leukemia–like disease and in BCR-ABL1-driven acute lymphoblastic leukemia (ALL). Although crizotinib binds to the ATP-binding site, it also allosterically affected the myristol binding pocket, the binding site of GNF2 and asciminib (former ABL001). Therefore, crizotinib has a seemingly unique double mechanism of action, on the ATP-binding site and on the myristoylation binding pocket. These findings strongly suggest the clinical evaluation of crizotinib for the treatment of advanced and therapy-resistant Ph+ leukemia.

scholarly journals Screening of Chloroquine, Hydroxychloroquine and Its Derivatives for Their Binding Affinity to Multiple SARS-CoV-2 Protein Drug Targets

2020 ◽  
Author(s):  
Mallikarjuna Nimgampalle ◽  
Vasudharani Devanthan ◽  
Ambrish Saxena
Keyword(s):  
Binding Affinity ◽  
In Silico ◽  
Drug Targets ◽  
Therapeutic Potential ◽  
Viral Proteins ◽  
Protein Drug ◽  
Potential Treatment ◽  
Health Authorities ◽  
Derivatives Of

Recently Chloroquine and its derivative Hydroxychloroquine have garnered enormous interest amongst the clinicians and health authorities’ world over as a potential treatment to contain COVID-19 pandemic. The present research aims at investigating the therapeutic potential of Chloroquine and its potent derivative Hydroxychloroquine against SARS-CoV-2 viral proteins. At the same time we have screened some chemically synthesized derivatives of Chloroquine and compared their binding efficacy with chemically synthesized Chloroquine derivatives through <i>in silico</i>approaches. For the purpose of the study, we have selected some essential viral proteins and enzymes implicated in SARS-CoV-2 replication and multiplication as putative drug targets.<br>

scholarly journals Variety, time of harvest and conditions during growing season have impact on red clover isoflavone content

2018 ◽  
Vol 27 (2) ◽  
Author(s):  
Eeva Arja Mustonen ◽  
Mikko Tuori ◽  
Päivi Kurki ◽  
Mika Isolahti ◽  
Juhani Taponen ◽  
...  
Keyword(s):  
High Performance ◽  
Trifolium Pratense ◽  
Red Clover ◽  
Weather Conditions ◽  
Biochanin A ◽  
Growing Seasons ◽  
Crop Varieties ◽  
Isoflavone Content ◽  
Trifolium Pratense L ◽  
Time Of Harvest

Red clover (Trifolium pratense L.) is the predominant legume used in northern European agriculture. Official red clover variety trials are conducted by Natural Resources Institute Finland (Luke) to determine the value of field crop varieties. The trials used for the current analysis were conducted in Luke units in southern Finland (Mikkeli) and northern Finland (Ruukki) in two consecutive years. Plant samples for isoflavone analyses were collected from four varieties grown as four replicates and harvested twice during both growing seasons. The four main isoflavones biochanin A, genistein, daidzein and formononetin were analysed using high performance liquid chromatography. Total phytoestrogen content in the varieties varied in the range of 11.2−14.8 mg g-1 dry matter (DM). The variety and the time of harvest had most effect on the isoflavone, especially formononetin, contents of red clover. A more northern growing area and challenging weather conditions were associated with increased isoflavone concentrations.

scholarly journals Energetics of carbohydrate binding by a 14 kDa S-type mammalian lectin

1995 ◽  
Vol 308 (1) ◽  
pp. 237-241 ◽  
Author(s):  
R Ramkumar ◽  
A Surolia ◽  
S K Podder
Keyword(s):  
Binding Constants ◽  
Van Der Waals Interactions ◽  
Titration Calorimetry ◽  
Carbohydrate Binding ◽  
Glucose Binding ◽  
The Stability ◽  
L 14 ◽  
Derivatives Of ◽  
Binding Lectin ◽  
Site Binding

The thermodynamics of the binding of derivatives of galactose and lactose to a 14 kDa beta-galactoside-binding lectin (L-14) from sheep spleen has been studied in 10 nM phosphate/150 mM NaCl/10 mM beta-mercaptoethanol buffer, pH 7.4, and in the temperature range 285-300 K using titration calorimetry. The single-site binding constants of various sugars for the lectin were in the following order: N-acetyl-lactosamine thiodigalactoside > 4-methylumbelliferyl lactoside > lactose > 4-methylumbelliferyl alpha-D-galactoside > methyl-alpha-galactose > methyl-beta-galactose. Reactions were essentially enthalpically driven with the binding enthalpies ranging from -53.8 kJ/mol for thiodigalactoside at 301 K to -2.2 kJ/mol for galactose at 300 K, indicating that hydrogen-bonding and van der Waals interactions provide the major stabilization for these reactions. However, the binding of 4-methylumbelliferyl-alpha-D-galactose displays relatively favourable entropic contributions, indicating the existence of a non-polar site adjacent to the galactose-binding subsite. From the increments in the enthalpies for the binding of lactose, N-acetyl-lactosamine and thiodigalactoside relative to methyl-beta-galactose, the contribution of glucose binding in the subsite adjacent to that for galactose shows that glucose makes a major contribution to the stability of L-14 disaccharide complexes. Observation of enthalpy-entropy compensation for the recognition of saccharides such as lactose by L-14 and the absence of it for monosaccharides such as galactose, together with the lack of appreciable changes in the heat capacity (delta Cp), indicate that reorganization of water plays an important role in these reactions.

Zur Biogenese der Isoflavone

1961 ◽  
Vol 16 (1) ◽  
pp. 2-5 ◽  
Author(s):  
Hans Grisebach ◽  
Gerhard Brandner
Keyword(s):  
Cicer Arietinum ◽  
Cinnamic Acid ◽  
Red Clover ◽  
Biochanin A ◽  
Cicer Arietinum L ◽  
The One

With the aid of cinnamic acid-[3-14C] and DL-Phenylalanine-[1-14C] it has been demonstrated that the biogenesis of both biochanin-A (5.7-Dihydroxy-4′-methoxyisoflavone) and formononetin (7-Hydroxy-4′-methoxyisoflavone) in chana germ (Cicer arietinum L.) involves a phenyl migration like the one which has been found to occur in the biogenesis of formononetin in red clover. 4.4′.6′-Trihydroxychalcone-4′-glucoside-[β-14C] is incorporated into formononetin but not into biochanin-A, the entire radioactivity being localized in C-2 of formononetin. Thus it has been proven that a C6-C3-C6 compound can be converted into an isoflavone. Acetate-[1-14C] is incorporated almost exclusively into ring A of formononetin.

scholarly journals Soluble Phenolic Compounds in Different Cultivars of Red Clover and Alfalfa, and their Implication for Protection against Proteolysis and Ammonia Production in Ruminants

2015 ◽  
Vol 10 (7) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Isabelle A. Kagan ◽  
Ben M. Goff ◽  
Michael D. Flythe
Keyword(s):  
Phenolic Compounds ◽  
Trifolium Pratense ◽  
Phenolic Content ◽  
Colorimetric Assay ◽  
Red Clover ◽  
Biochanin A ◽  
Total Phenolic ◽  
Ammonia Production ◽  
Response Factors ◽  
Soluble Phenolics

Red clover ( Trifolium pratense) contains soluble phenolic compounds with roles in inhibiting proteolysis and ammonia production. Alfalfa ( Medicago sativa) has been found to have a low phenolic content, but few alfalfa and red clover cultivars have been compared for phenolic content. Total soluble phenolics were quantified by a Folin-Ciocalteu colorimetric assay in nine red clover and 27 alfalfa cultivars. Mean total phenolic contents of red clover and alfalfa were 36.5 ± 4.3 mg/gdw and 15.8 ± 1.4 mg/gdw, respectively, with the greater standard deviation of red clover possibly indicating more diversity in phenolic content. Because different phenolic standards had different response factors in the colorimetric assay, the red clover and 11 alfalfa cultivars were analyzed by HPLC to determine if the differences in total soluble phenolics between genera reflected differences in the amounts of phenolics or in the classes of phenolics responding to the colorimetric assay. Two red clover cultivars differed in total phenolics and phaselic acid. Alfalfa produced different phenolic compounds from red clover, at lower concentrations. Extracts of two red clover cultivars were separated by thin-layer chromatography (TLC), and the bands were assayed for activity against Clostridium sticklandii, a bovine ruminal hyper ammonia-producing bacterium (HAB). Only biochanin A had anti-HAB activity. Inhibitory amounts indicated that five red clover cultivars could be suitable sources of anti-HAB activity.

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