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34 results on '"Flavone derivative"'

1. Designing fisetin nanocrystals for enhanced in cellulo anti-angiogenic and anticancer efficacy

Author

Panpan Ma, Johanne Seguin, Nhu Ky Ly, Luis Castillo Henríquez, Eva Plansart, Karim Hammad, Rabah Gahoual, Hélène Dhôtel, Charlotte Izabelle, Bruno Saubamea, Cyrille Richard, Virginie Escriou, Nathalie Mignet, and Yohann Corvis

Subjects
Flavone derivative, Solvent/antisolvent nanoprecipitation, Crystalline nanosuspension, Sustained drug release, In vitro evaluation, Pharmacy and materia medica, RS1-441
Abstract

We report the formulation, characterization, colloidal stability, and in vitro efficiency of Fisetin nanocrystals stabilized by poloxamer P407. Such nanocrystals present a nanometer scale (148.6 ± 1.1 nm) and a high homogeneity (polydispersity index of 0.17 ± 0.01), with a production yield of 97.0 ± 2.5%. The engineered formulations of nanocrystals suspension (pH of 7.4 ± 0.1), stabilized via steric repulsion, are stable for several days in aqueous environment (Milli Q water, NaCl 10 mM or mannitol 5% w/v), for few days in HEPES buffered saline (HBS) (20 / 150 mM) under sink conditions, and in culture medium. After freeze drying in 5% w/v mannitol, the nanocrystal formulations can be stored at −80 °C for at least 120 days. Drug release experiments displayed a 98.7 ± 5.1% cumulative release over 3 days in HBS. Compared to the free drug, the nanocrystal formulations showed an improved cytotoxicity highlighted by the decrease of the half maximal inhibitory concentration for both murine Lewis lung carcinoma (3LL) and human endothelial (EA.hy926) cell lines. In addition, after incubation with Fisetin nanosuspensions, significant changes in the cell morphology for both cell lines were observed, showing an improved anti-angiogenic effect of nanocrystals formulation compared to the free drug. Overall, Fisetin formulated as nanocrystals showed enhanced biopharmaceutical properties and in vitro activity, offering a wide range of indications for challenging applications in the clinic.

Published
2022
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2. Inhibition of Quorum-Sensing Regulator from Pseudomonas aeruginosa Using a Flavone Derivative.

Author

Xie, Yanxuan, Chen, Jingxin, Wang, Bo, Peng, Ai-Yun, Mao, Zong-Wan, and Xia, Wei

Subjects
*QUORUM sensing, *ESTER derivatives, *PHOSPHATE esters, *COLLECTIVE behavior, *PSEUDOMONAS aeruginosa, *DRUG resistance in bacteria, *FLAVONES
Abstract

Quorum sensing (QS) is a cell-to-cell communication process that controls bacterial collective behaviors. The QS network regulates and coordinates bacterial virulence factor expression, antibiotic resistance and biofilm formation. Therefore, inhibition of the QS system is an effective strategy to suppress the bacterial virulence. Herein, we identify a phosphate ester derivative of chrysin as a potent QS inhibitor of the human pathogen Pseudomonas aeruginosa (P. aeruginosa) using a designed luciferase reporter assay. In vitro biochemical analysis shows that the chrysin derivative binds to the bacterial QS regulator LasR and abrogates its DNA-binding capability. In particular, the derivative exhibits higher anti-virulence activity compared to the parent molecule. All the results reveal the potential application of flavone derivative as an anti-virulence compound to combat the infectious diseases caused by P. aeruginosa. [ABSTRACT FROM AUTHOR]

Published
2022
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3. A375 melanoma cells are sensitized to cisplatin-induced toxicity by a synthetic nitro-flavone derivative 2-(4-Nitrophenyl)-4H-chromen-4-one through inhibition of PARP1.

Author

Mitra, Anindita and Ghosh, Rita

Abstract

Background: Cisplatin has been extensively used in therapeutics for its broad-spectrum anticancer activity and frequently used for the treatment of solid tumors. However, it presents several side-effects and several cancers develop resistance. Combination therapy of cisplatin with poly (ADP-ribose) polymerase 1 (PARP1) inhibitors has been effective in increasing its efficacy at lower doses. Methods and results: In this work, we have shown that the nitro-flavone derivative, 2-(4-Nitrophenyl)-4H-chromen-4-one (4NCO), can improve the sensitivity of cancer cells to cisplatin through inhibition of PARP1. The effect of 4NCO on cisplatin toxicity was studied through combination therapy in both exponential and density inhibited A375 melanoma cells. Combination index (CI) was determined from isobologram analysis. The mechanism of cell killing was assessed by lactate dehydrogenase (LDH) assay. Temporal nicotinamide adenine dinucleotide (NAD+) assay was done to show the inhibition of PARP1. We also performed in silico molecular modeling studies to know the binding mode of 4NCO to a modeled PARP1-DNA complex containing cisplatin-crosslinked adduct. The results from both in silico and in cellulo studies confirmed that PARP1 inhibition by 4NCO was most effective in sensitizing A375 melanoma cells to cisplatin. Isobologram analysis revealed that 4NCO reduced cell viability both in exponential and density inhibited A375 cells synergistically. The combination led to cell death through apoptosis. Conclusion: The synthetic nitro-flavone derivative 4NCO effectively inhibited the important nuclear DNA repair enzyme PARP1 and therefore, could complement the DNA-damaging anticancer drug cisplatin in A375 cells and thus, could act as a potential adjuvant to cisplatin in melanoma therapy. [ABSTRACT FROM AUTHOR]

Published
2021
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4. Preferential interaction with c-MYC quadruplex DNA mediates the cytotoxic activity of a nitro-flavone derivative in A375 cells

Author

Anindita Mitra, Sudipta Bhowmik, and Rita Ghosh

Subjects
Flavone derivative, UV–Vis absorption spectroscopy, Fluorescence spectroscopy, Circular dichroism spectroscopy, Molecular docking, In cellulo studies, Chemistry, QD1-999
Abstract

G-quadruplex DNAs (G4 DNAs) are emerging as promising anticancer drug targets due to their presence in the promoter regions of different oncogenes. Utilizing different spectroscopic techniques like UV–Vis absorption titration, thermal denaturation, spectrofluorimetric titration, fluorescence displacement assay, Job plot analysis, circular dichroism spectroscopy and also, molecular docking studies, the interaction of a synthetic nitro-flavone, 2-(4-Nitrophenyl)-4H-chromen-4-one (4NCO), with various G4 DNA structures (c-KIT1, c-KIT2, c-MYC, h-TELO and VEGF) was elucidated. We also investigated the effect of 4NCO on different cancer cell lines. Effect on cell morphology, DNA damage, cell cycle arrest, viability and mode of cell death were evaluated in A375 melanoma cells. Our findings indicated that 4NCO showed preferential binding towards c-MYC promoter G4 to stabilize it with a binding constant (Kb) value of the order of ~105 M−1 and binding stoichiometry of ~1:1. It also showed a unique dual binding mode when bound to c-MYC with a lower binding free energy having multiple strong interactions when compared to the other G4s. In cells, it induced DNA damage resulting in cell cycle arrest at G1/S phase until 24 h, after which, cells strictly underwent apoptosis. It also showed a preferential cytotoxicity towards the A375 melanoma cells. The ability of 4NCO to stabilize the c-MYC G4 to possibly suppress the over-expression of MYC was responsible for inhibition of proliferation of these cells. Hence, these results present a novel finding on the effectiveness of the nitro-flavone derivative 4NCO as a potent ligand for c-MYC G4 DNA thereby, providing possibilities of its use in cancer therapy for regulating the oncogene expression in cancer cells.

Published
2021
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5. Inhibition of Quorum-Sensing Regulator from Pseudomonas aeruginosa Using a Flavone Derivative

Author

Yanxuan Xie, Jingxin Chen, Bo Wang, Ai-Yun Peng, Zong-Wan Mao, and Wei Xia

Subjects
Pseudomonas aeruginosa, quorum sensing, las system, flavone derivative, inhibitor, Organic chemistry, QD241-441
Abstract

Quorum sensing (QS) is a cell-to-cell communication process that controls bacterial collective behaviors. The QS network regulates and coordinates bacterial virulence factor expression, antibiotic resistance and biofilm formation. Therefore, inhibition of the QS system is an effective strategy to suppress the bacterial virulence. Herein, we identify a phosphate ester derivative of chrysin as a potent QS inhibitor of the human pathogen Pseudomonas aeruginosa (P. aeruginosa) using a designed luciferase reporter assay. In vitro biochemical analysis shows that the chrysin derivative binds to the bacterial QS regulator LasR and abrogates its DNA-binding capability. In particular, the derivative exhibits higher anti-virulence activity compared to the parent molecule. All the results reveal the potential application of flavone derivative as an anti-virulence compound to combat the infectious diseases caused by P. aeruginosa.

Published
2022
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6. Studies on the interaction of a synthetic nitro-flavone derivative with DNA: A multi-spectroscopic and molecular docking approach.

Author

Mitra, A., Saikh, F., Das, J., Ghosh, S., and Ghosh, R.

Subjects
*DNA, *MOLECULAR docking, *FLUORESCENCE, *FLAVONES
Abstract

Interaction of a ligand with DNA is often the basis of drug action of many molecules. Flavones are important in this regard as their structural features confer them the ability to bind to DNA. 2-(4-Nitrophenyl)-4H-chromen-4-one (4NCO) is an important biologically active synthetic flavone derivative. We are therefore interested in studying its interaction with DNA. Absorption spectroscopy studies included standard and reverse titration, effect of ionic strength on titration, determination of stoichiometry of binding and thermal denaturation. Spectrofluorimetry techniques included fluorimetric titration, quenching studies and fluorescence displacement assay. Assessment of relative viscosity and estimation of thermodynamic parameters from CD spectral studies were also undertaken. Furthermore, molecular docking analyses were also done with different short DNA sequences. The fluorescent flavone 4NCO reversibly interacted with DNA through partial intercalation as well as minor-groove binding. The binding constant and the number of binding sites were of the order 10 4  M −1 and 1 respectively. The binding stoichiometry with DNA was found to be 1:1. The nature of the interaction of 4NCO with DNA was hydrophobic in nature and the process of binding was spontaneous, endothermic and entropy-driven. The flavone also showed a preference for binding to GC rich sequences. The study presents a profile for structural and thermodynamic parameters, for the binding of 4NCO with DNA. DNA is an important target for ligands that are effective against cell proliferative disorders. In this regard, the molecule 4NCO is important since it can exert its biological activity through its DNA binding ability and can be a potential drug candidate. [ABSTRACT FROM AUTHOR]

Published
2018
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8. Crystal structure of 3-(4-methoxyphenyl)-2,3-dihydro-1H-naphtho[2,1-b]pyran-1-one

Author

R. Vasanthi, D. Reuben Jonathan, K. S. Elizhlarasi, B. K. Revathi, and G. Usha

Subjects
crystal structure, hydropyran, flavone derivative, Crystallography, QD901-999
Abstract

In the title compound, C20H16O3, the hydropyran ring adopts a distorted half-chair conformation with the methine C atom and the ring O atom displaced by −0.554 (2) and 0.158 (1) Å, respectively, from the plane of the other four atoms (r.m.s. deviation = 0.020 Å). Its mean plane (all atoms) is inclined to the naphthalene ring system at a dihedral angle of 11.67 (1)°. The dihedral angle between the napthalene ring system and the phenyl ring is 71.84 (1)°. In the crystal, no diectional interactions beyond van der Waals contacts could be identified.

Published
2015
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9. Crystal structure of (2S/2R,3S/3R)-3-hydroxy-2-phenylchroman-4-one

Author

Roumaissa Belguedj, Sofiane Bouacida, Hocine Merazig, Aissa Chibani, and Abdelmalek Bouraiou

Subjects
crystal structure, flavone derivative, hydrogen bonds, C—H...π interactions, Crystallography, QD901-999
Abstract

In the title molecule, C15H12O3, the C atoms bearing the hydroxy group and the phenyl ring are disordered over two sets of sites with refined occupancies of 0.573 (7) and 0.427 (7). There is also disorder of the phenyl ring but the hydroxy group was refined as ordered. The dihedral angles between the benzene ring of the chromane ring system and the phenyl ring are 89.7 (2)° for the major component of disorder and 72.1 (3)° for the minor component. Both disorder components of the the dihydropyran ring are in a half-chair conformation. In the crystal, molecules are linked by pairs of O—H...O hydrogen bonds, forming inversion dimers with an R22(10) graph-set motif. Weak C—H...π interactions link these dimers into ladders along [001].

Published
2015
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10. Assay method for quality control and stability studies of a new anti-diabetic and anti-dyslipidemic flavone (S002-853).

Author

Naqvi, Arshi, Pandey, Anuja, Gupta, Varsha, Malasoni, Richa, Srivastava, Akansha, Pandey, Rishi Ranjan, Satyanarayana, M., Pratap, Ram, and Dwivedi, Anil Kumar

Subjects
*FLAVONES, *HYPOGLYCEMIC agents, *DYSLIPIDEMIA, *HIGH performance liquid chromatography
Abstract

Background: Flavonoid-rich extract of the plant is long known for its anti-diabetic activities in traditional medicine. S002-853, a new flavone derivative synthesized by Central Drug Research Institute (CDRI) has been used for the present study. Objectives: The present study aimed at development of an assay method for quality control (QC) and stability studies of a new anti-diabetic and anti-dyslipidemic agent CDRI compound S002-853. Materials and Methods: A validated high-performance liquid chromatography analysis method for S002-853 was developed for in process QC and stability studies. The separation was achieved on a RP-C18 (25 cm x 0.4 cm, 5 μm, Phenomenex) at 240 nm with flow rate of 1.0 ml/min. This method was applied successfully in establishing forced degradation and drug-excipient testing protocols as per International Conference on Harmonization guidelines. Results: The result of estimation and stress testing studies indicated a high degree of selectivity of this method. S002-853 was most stable at pH 7 and under photolytic conditions. The temperature degradation pattern of S002-853 was found tofollow the zero order degradation. Conclusion: The method described is easy and simple hence can be easily reproduced. This method can be very useful for bulk manufacture QC, and drug development process. [ABSTRACT FROM AUTHOR]

Published
2015
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11. Designing fisetin nanocrystals for enhanced in cellulo anti-angiogenic and anticancer efficacy.

Author

Ma P, Seguin J, Ly NK, Henríquez LC, Plansart E, Hammad K, Gahoual R, Dhôtel H, Izabelle C, Saubamea B, Richard C, Escriou V, Mignet N, and Corvis Y

Abstract

We report the formulation, characterization, colloidal stability, and in vitro efficiency of Fisetin nanocrystals stabilized by poloxamer P407. Such nanocrystals present a nanometer scale (148.6 ± 1.1 nm) and a high homogeneity (polydispersity index of 0.17 ± 0.01), with a production yield of 97.0 ± 2.5%. The engineered formulations of nanocrystals suspension (pH of 7.4 ± 0.1), stabilized via steric repulsion, are stable for several days in aqueous environment (Milli Q water, NaCl 10 mM or mannitol 5% w/v), for few days in HEPES buffered saline (HBS) (20 / 150 mM) under sink conditions, and in culture medium. After freeze drying in 5% w/v mannitol, the nanocrystal formulations can be stored at -80 °C for at least 120 days. Drug release experiments displayed a 98.7 ± 5.1% cumulative release over 3 days in HBS. Compared to the free drug, the nanocrystal formulations showed an improved cytotoxicity highlighted by the decrease of the half maximal inhibitory concentration for both murine Lewis lung carcinoma (3LL) and human endothelial (EA.hy926) cell lines. In addition, after incubation with Fisetin nanosuspensions, significant changes in the cell morphology for both cell lines were observed, showing an improved anti-angiogenic effect of nanocrystals formulation compared to the free drug. Overall, Fisetin formulated as nanocrystals showed enhanced biopharmaceutical properties and in vitro activity, offering a wide range of indications for challenging applications in the clinic., Competing Interests: None., (© 2022 The Authors.)

Published
2022
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13. Thermal behavior of some vanadyl complexes with flavone derivatives as potential insulin-mimetic agents.

Author

Badea, Mihaela, Olar, Rodica, Uivarosi, Valentina, Marinescu, Dana, Aldea, Victoria, Barbuceanu, Stefania, and Nitulescu, George

Subjects
*THERMAL analysis, *VANADATES, *FLAVONOIDS, *LIGANDS (Biochemistry), *METAL ions, *STABILITY (Mechanics), *STEREOCHEMISTRY, *METAL complexes
Abstract

Two new complexes having general formula VOL· nHO [( 1) L: 5-hydroxyflavone, n = 1; ( 2) L: chrysin, n = 4] were synthesized and characterized. Based on IR and electronic data we concluded that studied flavones act as bidentate ligands in complexes with metallic ion coordinated in a square-pyramidal stereochemistry. The thermal analysis (TG, DTA) elucidated the composition and also the number and nature of the water molecules. The thermal behavior also indicated strong interactions between oxovanadium (IV) and these oxygen donor ligands. [ABSTRACT FROM AUTHOR]

Published
2011
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14. QSAR, action mechanism and molecular design of flavone and isoflavone derivatives with cytotoxicity against HeLa

Author

Liao, Si Yan, Chen, Jin Can, Qian, Li, Shen, Yong, and Zheng, Kang Cheng

Subjects
*HELA cells, *QSAR models, *CELL-mediated cytotoxicity, *CELL lines, *DENSITY functionals, *CANCER cell growth
Abstract

Abstract: The quantitative structure–activity relationship (QSAR) of 32 flavone and isoflavone derivatives with cytotoxicity expressed as pGC50, which is defined as the negative value of the logarithm of necessary molar concentration of this series of compounds to cause 50% growth inhibition against the human cervical epithelioid carcinoma cell line (HeLa), has been studied by using the density functional theory (DFT), molecular mechanics (MM2) and statistical methods. In order to obtain QSAR model with high predictive ability, the original dataset was randomly divided into a training set comprising 26 compounds and a test set comprising the rest 6 compounds. An optimal model for the training set with significant statistical quality () and predictive ability (q 2 =0.818) was established. The same model was further applied to predict pGC50 values of the 6 compounds in the test set, and the resulting predictive correlation coefficient reaches 0.738, further showing that this QSAR model has high predictive ability. It is very interesting to find that the cytotoxicities of these compounds against HeLa appear to be mainly governed by two quantum-chemical factors, i.e., the energy (E LUMO) of the lowest unoccupied molecular orbital (LUMO) and the net charges of C atom at site 6 on aromatic rings (Q C6). Here the possible action mechanism of these compounds was analyzed and discussed in detail, in particular, the fact why the flavone derivatives have considerably higher cytotoxicity than isoflavone derivatives was reasonably explained. Based on this QSAR equation, 5 new compounds with higher cytotoxicity have been theoretically designed. Such results can offer useful theoretical references for experimental works. [Copyright &y& Elsevier]

Published
2008
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15. Mechanism of interaction of a flavone derivative with halides: Basis set dependence of the theoretical results

Author

Sarkar, Moloy and Samanta, Anunay

Subjects
*FLUORIDES, *GEOMETRY, *QUANTUM chemistry, *PHYSICAL & theoretical chemistry
Abstract

Abstract: Density functional calculations have been carried out with a view to obtain an understanding of the mechanism of the fluoride-selective signaling behavior of a flavone-based chemosensor. Parameters such as the initial geometry and basis set are found to be important factors in predicting the mechanism of the signaling event. It is shown that the calculations employing a higher basis set comprising diffused and polarization functions do not always lead to results that are meaningful. [Copyright &y& Elsevier]

Published
2008
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16. QSAR modeling of the interaction of flavonoids with GABA(A) receptor

Author

Duchowicz, Pablo R., Vitale, Martín G., Castro, Eduardo A., Autino, Juan C., Romanelli, Gustavo P., and Bennardi, Daniel O.

Subjects
*FLAVONOIDS, *LIGANDS (Biochemistry), *BENZODIAZEPINES, *MOLECULAR structure, *QSAR models
Abstract

Abstract: Experimentally assigned values to binding affinity constants of flavonoid ligands towards the benzodiazepine site of the GABA(A) receptor complex were compiled from several publications, and enabled to perform a predictive analysis based on Quantitative Structure–Activity Relationships (QSAR). The best linear model established on 78 molecular structures incorporated four molecular descriptors, selected from more than a thousand of geometrical, topological, quantum-mechanical and electronic types of descriptors and calculated by Dragon software. An application of this QSAR equation was performed by estimating the binding affinities for some newly synthesized flavonoids displaying 2-,7-substitutions in the benzopyrane backbone which still do not have experimentally measured potencies. [Copyright &y& Elsevier]

Published
2008
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17. QSAR prediction of inhibition of aldose reductase for flavonoids

Author

Mercader, Andrew G., Duchowicz, Pablo R., Fernández, Francisco M., Castro, Eduardo A., Bennardi, Daniel O., Autino, Juan C., and Romanelli, Gustavo P.

Subjects
*MOLECULAR structure, *GENETIC algorithms, *COMBINATORIAL optimization, *FLAVONOIDS
Abstract

Abstract: We performed a predictive analysis based on quantitative structure–activity relationships (QSAR) of an important property of flavonoids, which is the inhibition (IC50) of aldose reductase (AR). The importance of AR inhibition is that it prevents cataract formation in diabetic patients. The best linear model constructed from 55 molecular structures incorporated six molecular descriptors, selected from more than a thousand geometrical, topological, quantum-mechanical, and electronic types of descriptors. As a practical application, we used the obtained QSAR model to predict the AR inhibitory effect of newly synthesized flavonoids that present 2-, 7-substitutions in the benzopyrane backbone. [Copyright &y& Elsevier]

Published
2008
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18. Glucosylation of Phenolic Compounds by Pharbitis nil Hairy Roots: I. Glucosylation of Coumarin and Flavone Derivatives.

Author

Kanho, Hideki, Yaoya, Sayaka, Itani, Tomio, Nakane, Takahisa, Kawahara, Nobuo, Takase, Yoichi, Masuda, Kazuo, and Kuroyanagi, Masanori

Subjects
*JAPANESE morning glory, *COUMARINS, *PLANT growing media, *METABOLITES, *BIOTRANSFORMATION (Metabolism), *PHENOLS
Abstract

Examines the potent glucosylation activity of the hairy roots of medicinal morning glory, Pharbitis nil, against umbelliferone and aesculetin. Provision of a potential plant culture system for the production of useful secondary metabolites and research into the secondary metabolism and biotransformation of substrates; Capability of hairy roots against some phenolic compounds; Conversion of incubated coumarin and flavone derivatives by the hairy roots.

Published
2004
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19. Antifungal activity of extracts and phenolic compounds from Deguelia duckeana

Author

Lorena M. Cursino-Hron, Cecilia Veronica Nunez, João Vicente Braga de Souza, Jane V.N. Marinho, André C. de Oliveira, Alita Moura de Lima, and Nerilson M. Lima

Subjects
Phytochemistry, Lignan, Cytotoxicity, Flavonoid, lcsh:RS1-441, 3,4,7 Trimethoxyflavone, 5,4 Dihydroxy Isolonchocarpine, 01 natural sciences, Chalcone, Chalcone Derivative, General Pharmacology, Toxicology and Pharmaceutics, Candida albicans, Timbó, chemistry.chemical_classification, biology, Traditional medicine, 3,5,4 Trimethoxy Stilbene, Corpus albicans, Amazonian plant, 3,5,4 Trimethoxy 4 Prenylstilbene, 3,4,7 Trimethoxy Flavonol, Phytochemical, Flavone Derivative, Minimum Inhibitory Concentration, Anti-fungal Activity, 4 Hydroxylonchocarpine, Cryptococcus Neoformans, Carbon Nuclear Magnetic Resonance, 3,4 Methylenedioxy 7 Methoxyflavone, Plant Extract, Deguelia Duckeana, lcsh:Pharmacy and materia medica, Minimum inhibitory concentration, Unclassified Drug, medicine, 4 Hydroxyderricidine, Cryptococcus gattii, Cryptococcus neoformans, Liquid Chromatography-mass Spectrometry, Derricidine, 010405 organic chemistry, 010401 analytical chemistry, biology.organism_classification, medicine.disease, Nonhuman, 0104 chemical sciences, Cryptococcus Gattii, chemistry, Stilbene, Cryptococcosis, Deguelia Duckeana Extract, Proton Nuclear Magnetic Resonance, Plant Medicinal Product, Yangambin, 4 Hydroxyderricine
Abstract

Candida spp. is associated with almost 80% of all nosocomial fungal infections and is considered a major cause of blood stream infections. In humans, Cryptococcosis is a disease of the lungs caused by the fungi Cryptococcus gattii and Cryptococcus neoformans. It can be potentially fatal, especially in immune-compromised patients. In a search for antifungal drugs, Deguelia duckeana extracts were assayed against these two fungi and also against Candida albicans, which causes candidiasis. Hexane branches and CH2Cl2 root extracts as well as the substances 4-hydroxylonchocarpine, 3,5,4′-trimethoxy-4-prenylstilbene and 3′,4′-methylenedioxy-7-methoxyflavone were assayed to determine the minimal inhibitory concentration. Phytochemical study of CH2Cl2 root and hexane branch extracts from D. duckeana A.M.G. Azevedo, Fabaceae, resulted in the isolation and characterization of nine phenolic compounds: 4-hydroxyderricine, 4-hydroxylonchocarpine, 3′,4′,7-trimethoxy-flavonol, 5,4′-dihydroxy-isolonchocarpine, 4-hydroxyderricidine, derricidine, 3,5,4′-trimethoxy-stilbene, 3′,4′,7-trimethoxyflavone and yangambin. The only active extract was a CH2Cl2 root showing minimal inhibitory concentration 800 μg/ml against C. gattii, and the investigation of compounds obtained from this extract showed that 4-hydroxylonchocarpine was active against all three fungi (C. neoformans, C. gattii and C. albicans). These results suggest that D. duckeana extracts have potential therapeutic value for the treatment of pathogenic fungi. Keywords: Amazonian plant, Chalcone, Flavonoid, Lignan, Stilbene, Timbó

Published
2018

20. Medical compounds

Author

PITARI, Giovanni Mario, LEOTTA, Claudia Giovanna, DRAGO, Carmelo, and NICOLOSI, Giovanni

Subjects
malignant tumours, flavone derivative
Published
2017

21. Caspase-Independent Pathways of Programmed Cell Death: The Unraveling of New Targets of Cancer Therapy?

Author

Constantinou, Constantina, Papas, Konstantinos A., Constantinou, Andreas I., and Constantinou, Andreas I. [0000-0003-0365-1821]

Subjects
carcinoid, chm 1, cell organelle, vitamin D, Apoptosis, quinolone derivative, serine proteinase, Drug Discovery, advanced cancer, mitochondrion, Programmed cell death, Drug discovery, leukemia, clinical trial, Calpain, Cell biology, myeloma, Oncology, Caspases, calpain, signal transduction, protein Bax, receptor down regulation, Proteases, drug design, phenol derivative, caspase, 2' fluoro 6,7 methylenedioxy 2 phenyl 4 quinolone, Antineoplastic Agents, Necrosis, estradiol, unindexed drug, otorhinolaryngologic diseases, Humans, cathepsin, human, protein Bid, drug inhibition, apoptosis inducing factor, Pharmacology, drug targeting, rb 49, tumor resistance, protein phosphorylation, respiratory tract diseases, drug efficacy, herbaceous agent, paclitaxel poliglumex, flavopiridol, monoclonal antibody, molecular interaction, n methylpiperidinyl chlorophenyl flavone, solid tumor, benzyloxycarbonylvalylalanylaspartyl fluoromethyl ketone, mediator, Apoptosis Regulatory Proteins, Cancer Research, atiprimod, Mitochondrion, protein induction, AIF, Drug Delivery Systems, Caspase-independent cell death, oxidative stress, flavone derivative, bzl 101, receptor upregulation, antineoplastic agent, Caspase, AIF inhibitor, apoptosis inhibitor, Clinical Trials as Topic, biology, lung non small cell cancer, prostate cancer, unclassified drug, Mitochondria, cell death, cytotoxicity, rb 110, drug potency, Signal Transduction, liver cell carcinoma, animal structures, colecalciferol, regulatory mechanism, chromatin condensation, review, antineoplastic activity, tumor cell, Models, Biological, breast cancer, azaspirane, drug mechanism, Chemotherapy, Cathepsin, carcinogenic activity, nonhuman, 2,4,6 triiodophenol, cy 103, caspase inhibitor, gene expression, biology.protein, Cancer research, bobel 24, neoplasm, Peptide Hydrolases
Abstract

In the past few years, accumulating evidence in the literature supports the existence of pathways of caspase-independent programmed cell death (CI-PCD). These pathways are likely to be acting as 'death backup systems' that ensure effective removal of defective cells from the organism. Similar to classical apoptosis i.e. caspase-dependent programmed cell death (CD-PCD), the mitochondrion is the main organelle orchestrating the series of events which are required for the induction of CI-PCD. In addition, the pro-apoptotic proteins Bax and Bid are also key participants in CI-PCD. However, contrary to CD-PCD, CI-PCD involves executioners other than the caspases which include the cathepsins, the calpains and serine proteases. The protein AIF may also play an important role in the induction of CI-PCD. In this review we report current knowledge on CI-PCD and provide evidence for its regulation by chemotherapeutic agents currently used in the clinic and under investigation in clinical trials. Lastly, we discuss how the study of natural and synthetic agents triggering CI-PCD may help in the pharmacological design of a new generation of more effective chemotherapeutic drugs. The use of such drugs activating both CD-PCD and CI-PCD pathways should achieve a more successful eradication of carcinogenic cells and the attainment of lower levels of tumor resistance. © 2009 Bentham Science Publishers Ltd. 9 717 728 Tradenames: azaspirane bzl 101 chm 1 cy 103 rb 110 rb 49 xyotax Cited By :47

Published
2009
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22. Phenolic constituents with neuroprotective activities from Hypericum wightianum.

Author

Yang, Ling, Wang, Zi-Ming, Wang, Yun, Li, Rong-Sheng, Wang, Fei, and Wang, Kou

Subjects
*HYPERICUM, *PHENOLS, *GLYCOSIDES, *PLANT extracts
Abstract

Five undescribed phenolic compounds, inclusing a depsidone derivative, hyperwightin A, a flavone derivative, hyperwightin B, and three benzophenone glycosides, hyperwightins C-E, along with four known ones were isolated from the 95% EtOH extract of the whole plants of Hypericum wightianum. Structures of the obtained compounds were elucidated by spectroscopic analyses. The protective effects of the isolates against corticosterone-induced PC12 cell injury were assessed. Hyperwightin E, petiolin G and hyperxanthone exhibited noticeable neuroprotection at 10 μM. Image 108 • Five undescribed phenolic constituents were isolated from the whole plant of Hypericum wightianum. • Three compounds exhibited noticeable neuroprotection against corticosterone-induced PC12 cell injury. • Hyperwightin A represents the second report of depsidones in the genus Hypericum. [ABSTRACT FROM AUTHOR]

Published
2019
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23. Crystal structure of (2S/2R,3S/3R)-3-hydroxy-2-phenylchroman-4-one

Author

Aissa Chibani, Hocine Merazig, Roumaissa Belguedj, Sofiane Bouacida, and Abdelmalek Bouraiou

Subjects
crystal structure, Chemistry, Hydrogen bond, education, General Chemistry, Crystal structure, Dihedral angle, C—H⋯π inter­actions, Condensed Matter Physics, Ring (chemistry), Bioinformatics, Data Reports, Crystal, lcsh:Chemistry, chemistry.chemical_compound, Crystallography, C—H...π interactions, lcsh:QD1-999, Group (periodic table), hydrogen bonds, Chromane, flavone derivative, General Materials Science, Benzene
Abstract

In the title molecule, C15H12O3, the C atoms bearing the hydroxy group and the phenyl ring are disordered over two sets of sites with refined occupancies of 0.573 (7) and 0.427 (7). There is also disorder of the phenyl ring but the hydroxy group was refined as ordered. The dihedral angles between the benzene ring of the chromane ring system and the phenyl ring are 89.7 (2)° for the major component of disorder and 72.1 (3)° for the minor component. Both disorder components of the the dihydropyran ring are in a half-chair conformation. In the crystal, molecules are linked by pairs of O—H...O hydrogen bonds, forming inversion dimers with anR22(10) graph-set motif. Weak C—H...π interactions link these dimers into ladders along [001].

Published
2015

24. QSAR prediction of inhibition of aldose reductase for flavonoids

Author

Daniel Oscar Bennardi, Francisco M. Fernández, Andrew G. Mercader, Pablo R. Duchowicz, Eduardo A. Castro, Gustavo P. Romanelli, and Juan Carlos Autino

Subjects
Aldose reductase inhibition, Stereochemistry, Flavone derivative, Físico-Química, Ciencia de los Polímeros, Electroquímica, Clinical Biochemistry, Pharmaceutical Science, Quantitative Structure-Activity Relationship, Biochemistry, Aldehyde Reductase, Predictive Value of Tests, Drug Discovery, Cataract prevention, Computer Simulation, Molecular Biology, Replacement method, Flavonoids, Molecular Structure, Chemistry, QSAR, Flavone derivatives, Enhanced replacement method, Organic Chemistry, Ciencias Químicas, Dragon molecular descriptors, Genetic algorithm, Molecular Medicine, Humanities, CIENCIAS NATURALES Y EXACTAS
Abstract

We performed a predictive analysis based on quantitative structure–activity relationships (QSAR) of an important property of flavonoids, which is the inhibition (IC50) of aldose reductase (AR). The importance of AR inhibition is that it prevents cataract formation in diabetic patients. The best linear model constructed from 55 molecular structures incorporated six molecular descriptors, selected from more than a thousand geometrical, topological, quantum-mechanical, and electronic types of descriptors. As a practical application, we used the obtained QSAR model to predict the AR inhibitory effect of newly synthesized flavonoids that present 2-, 7-substitutions in the benzopyrane backbone50) of aldose reductase (AR). The importance of AR inhibition is that it prevents cataract formation in diabetic patients. The best linear model constructed from 55 molecular structures incorporated six molecular descriptors, selected from more than a thousand geometrical, topological, quantum-mechanical, and electronic types of descriptors. As a practical application, we used the obtained QSAR model to predict the AR inhibitory effect of newly synthesized flavonoids that present 2-, 7-substitutions in the benzopyrane backbone Fil: Mercader, Andrew Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina Fil: Duchowicz, Pablo Román. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina Fil: Fernández, Francisco Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina Fil: Castro, Eduardo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina Fil: Bennardi, Daniel Oscar. Universidad Nacional de La Plata. Facultad de Ciencias Agrarias y Forestales. Departamento de Ciencias Exactas. Cátedra de Química Orgánica; Argentina Fil: Autino, Juan Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Agrarias y Forestales. Departamento de Ciencias Exactas. Cátedra de Química Orgánica; Argentina Fil: Romanelli, Gustavo Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Ciencias Aplicadas "Dr. Jorge J. Ronco". Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Ciencias Aplicadas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Agrarias y Forestales. Departamento de Ciencias Exactas. Cátedra de Química Orgánica; Argentina

Published
2008

25. Compostos fenólicos e atividade antioxidante de Leiothrix flavescens (Bong.) Ruhland (Eriocaulaceae)

Author

Silva, M. A., Sumitami, J. S. A., Wagner Vilegas, Santos, Lourdes Campaner Dos, and Universidade Estadual Paulista (Unesp)

Subjects
infrared spectrometry, spectrophotometer, HSCCC, phenol derivative, lcsh:RS1-441, antioxidant activity, reduction, plant taxonomy, electrospray mass spectrometry, lcsh:Pharmacy and materia medica, Leiothrix flavascens extract, counter current chromatography, flavone derivative, luteolin, 6 methoxyluteolin, methanol, nuclear magnetic resonance spectroscopy, apigenin, Leiothrix, folin ciocalteau assay, flower head, drug identification, 1,3 di o feruloylglycerol, assay, unclassified drug, 1,1 diphenyl 2 picrylhydrazyl, herb, lcsh:HD9665-9675, Eriocaulaceae, lcsh:Pharmaceutical industry, plant extract, eriocaulaceae, leiothrix, hsccc, atividade antioxidante, Leiothrix flavascens
Abstract

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:22:42Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:29:58Z : No. of bitstreams: 1 2-s2.0-50049129964.pdf: 74371 bytes, checksum: cf75aa12221b3889c121408fba1f3951 (MD5) Made available in DSpace on 2014-05-27T11:22:43Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-12-01 O presente estudo químico foi realizado com extrato metanólico de Leiothrix flavescens (Bong.) Ruhland (Eriocaulaceae) por HSCCC. Fracionamento do extrato metanólico dos capítulos de L. flavescens por métodos cromatográficos preparativos e identificação das substâncias isoladas por (IV, UV, RMN) forneceu as flavonas apigenina, luteolina e 6-metoxiluteolina e o 1,3-di-Oferuloilglicerol. O extrato metanólico de L. flavescens foi avaliado quanto à sua atividade antioxidante utilizando- se o reagente de DPPH, enquanto que a quantificação de fenóis totais foi determinada utilizando-se o reagente de Folin-Ciocalteau. Os resultados evidenciaram que o extrato metanólico dos capítulos L. flavescens possui uma significativa atividade antioxidante. Estes resultados permitiram aprofundar a discussão taxonômica da família Eriocaulaceae. Palavras-chave: Eriocaulaceae; Leiothrix; HSCCC; atividade antioxidante. This paper describes a chemical investigation (by high-speed counter-current chromatography) of an extract in methanol of the capitula (flower-heads) of the endemic Brazilian herb Leiothrix flavescens (Bong.) Ruhland (Eriocaulaceae). Fractionation of this extract by preparative chromatography and identification of the isolated compounds by spectrometric methods (IR, UV, ESI-MS, NMR) led to the identification of flavones (apigenin, luteolin and 6-methoxyluteolin) and 1,3-di-O-feruloyl glycerol. The antioxidant activity of the extract was determined by DPPH reduction and the total phenolic content by the Folin-Ciocalteau assay. It was found that the methanolic extract of L. flavescens possesses strong antioxidant activity. Additionally, the chemical profile provided useful data for a discussion of the taxonomy of the Eriocaulaceae. Departamento de Quimica Orgânica Instituto de Química Universidade Estadual Paulista, UNESP, Araraquara, SP Departamento de Química Orgânica Instituto de Química Universidade Estadual Paulista, UNESP, Rua Francisco Degni, s/no, CEP: 14801-970 - Araraquara - SP Departamento de Quimica Orgânica Instituto de Química Universidade Estadual Paulista, UNESP, Araraquara, SP Departamento de Química Orgânica Instituto de Química Universidade Estadual Paulista, UNESP, Rua Francisco Degni, s/no, CEP: 14801-970 - Araraquara - SP

Published
2007

26. QSAR modeling of the interaction of flavonoids with GABA(A) receptor

Author

Martín Gustavo Vitale, Pablo R. Duchowicz, Eduardo A. Castro, Gustavo Pablo Romanelli, Daniel Oscar Bennardi, and Juan Carlos Autino

Subjects
Receptor complex, Quantitative structure–activity relationship, Molecular model, Stereochemistry, DRAGON MOLECULAR DESCRIPTORS, Quantitative Structure-Activity Relationship, Molecular descriptor, Drug Discovery, GABA(A), Binding site, Binding affinities, Pharmacology, Flavonoids, Binding Sites, Molecular Structure, Chemistry, GABAA receptor, QSAR, Otras Ciencias Químicas, Organic Chemistry, Ciencias Químicas, General Medicine, FLUNITRAZEPAM, Ligand (biochemistry), Receptors, GABA-A, FLAVONE DERIVATIVE, BENZODIAZEPINE RECEPTOR, REPLACEMENT METHOD, CIENCIAS NATURALES Y EXACTAS, Protein Binding
Abstract

Experimentally assigned values to binding affinity constants of flavonoid ligands towards the benzodiazepine site of the GABA(A) receptor complex were compiled from several publications, and enabled to perform a predictive analysis based on Quantitative Structure-Activity Relationships (QSAR). The best linear model established on 78 molecular structures incorporated four molecular descriptors, selected from more than a thousand of geometrical, topological, quantum-mechanical and electronic types of descriptors and calculated by Dragon software. An application of this QSAR equation was performed by estimating the binding affinities for some newly synthesized flavonoids displaying 2-,7-substitutions in the benzopyrane backbone which still do not have experimentally measured potencies. Fil: Duchowicz, Pablo Román. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina Fil: Vitale, Martin Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina Fil: Castro, Eduardo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina Fil: Autino, Juan Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Agrarias y Forestales; Argentina Fil: Romanelli, Gustavo Pablo. Universidad Nacional de La Plata. Facultad de Ciencias Agrarias y Forestales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Ciencias Aplicadas "Dr. Jorge J. Ronco". Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Ciencias Aplicadas; Argentina Fil: Bennardi, Daniel Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Ciencias Aplicadas "Dr. Jorge J. Ronco". Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Ciencias Aplicadas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Agrarias y Forestales; Argentina

Published
2007

27. Crystal structure of 3-(4-meth­oxy­phen­yl)-2,3-di­hydro-1H-naphtho­[2,1-b]pyran-1-one

Author

D. Reuben Jonathan, R. Vasanthi, B.K. Revathi, G. Usha, and K. S. Elizhlarasi

Subjects
crystal structure, Crystallography, Chemistry, General Chemistry, Crystal structure, Dihedral angle, Condensed Matter Physics, Ring (chemistry), Data Reports, Crystal, symbols.namesake, chemistry.chemical_compound, hydro­pyran, Pyran, QD901-999, Atom, symbols, flavone derivative, General Materials Science, van der Waals force, hydropyran, Naphthalene
Abstract

In the title compound, C20H16O3, the hydropyran ring adopts a distorted half-chair conformation with the methine C atom and the ring O atom displaced by −0.554 (2) and 0.158 (1) Å, respectively, from the plane of the other four atoms (r.m.s. deviation = 0.020 Å). Its mean plane (all atoms) is inclined to the naphthalene ring system at a dihedral angle of 11.67 (1)°. The dihedral angle between the napthalene ring system and the phenyl ring is 71.84 (1)°. In the crystal, no diectional interactions beyond van der Waals contacts could be identified.

Published
2015

28. Structural requirements for the flavonoid-mediated modulation of glutathione S-transferase P1-1 and GS-X pump activity in MCF7 breast cancer cells

Subjects
Drug Resistance, IC50, animal cell, quercetin, taxifolin, myricetin, glutathione transferase, toxicokinetics, lipophilicity, flavone derivative, heterocyclic compounds, eriodictyol, Biology Toxicology, chemical bond, multidrug resistance protein 1, enzyme inhibition, multidrug resistance protein 2, flavanoid, Cultured, article, food and beverages, Glutathione, CDNB, unclassified drug, enzyme activity, Tumor Cells, Isoenzymes, GS-X, priority journal, S-(2, Multidrug Resistance-Associated Proteins, Multiple, drug potency, MRP, Breast Neoplasms, Physiological Sciences, hydroxyl group, 50% inhibition concentration, Multidrug resistance associated protein, Structure-Activity Relationship, breast cancer, drug activity, catechin, DNP-SG, Membrane Transport Modulators, GSH, 3', Humans, controlled study, human, GST, luteolin, 4-dinitrophenyl)glutathione, structure activity relation, Flavonoids, galanin, kaempferol, nonhuman, 1-chloro-2, Glutathione conjugate, carbon, catechol derivative, human cell, fungi, Membrane Transport Proteins, IC 50, Biological Transport, 4-dinitrobenzene, morin, Glutathione S-transferase, cell strain MCF 7, Glutathione S-Transferase pi, P-gp, Neoplasm, genetic transfection, Carrier Proteins, 4' dihydroxyflavone
Abstract

The objective of this study was to investigate the structural requirements necessary for inhibition of glutathione S-transferase P1-1 (GSTP1-1) and GS-X pump (MRP1 and MRP2) activity by structurally related flavonoids, in GSTP1-1 transfected MCF7 cells (pMTG5). The results reveal that GSTP1-1 activity in MCF7 pMTG5 cells can be inhibited by some flavonoids. Especially galangin was able to inhibit almost all cellular GSTP1-1 activity upon exposure of the cells to a concentration of 25μM. Other flavonoids like kaempferol, eriodictyol and quercetin showed a moderate GSTP1-1 inhibitory potential. For GSTP1-1 inhibition, no specific structural requirements necessary for potent inhibition could be defined. Most flavonoids appeared to be potent GS-X transport inhibitors with IC50 values ranging between 0.8 and 8μM. Luteolin and quercetin were the strongest inhibitors with IC50 values of 0.8 and 1.3μM, respectively. Flavonoids without a C2-C3 double bond like eriodictyol, taxifolin and catechin did not inhibit GS-X pump activity. The results of this study demonstrate that the structural features necessary for high potency GS-X pump inhibition by flavonoids are (1) the presence of hydroxyl groups, especially two of them generating the 3′,4′- catechol moiety; and (2) a planar molecule due to the presence of a C2-C3 double bond. Other factors, like lipophilicity and the total number of hydroxyl groups do not seem to be dominating the flavonoid-mediated GS-X pump inhibition. To identify the GS-X pump responsible for the DNP-SG efflux in MCF7 cells, the effects of three characteristic flavonoids quercetin, flavone and taxifolin on MRP1 and MRP2 activity were studied using transfected MDCKII cells. All three flavonoids as well as the typical MRP inhibitor (MK571) affected MRP1-mediated transport activity in a similar way as observed in the MCF7 cells. In addition, the most potent GS-X pump inhibitor in the MCF7 cells, quercetin, did not affect MRP2-mediated transport activity. These observations clearly indicate that the GS-X pump activity in the MCF7 cells is likely to be the result of flavonoid-mediated inhibition of MRP1 and not MRP2. Altogether, the present study reveals that a major site for flavonoid interaction with GSH-dependent toxicokinetics is the GS-X pump MRP1 rather than the conjugating GSTP1-1 activity itself. Of the flavonoids shown to be most active especially quercetin is frequently marketed in functional food supplements. Given the physiological levels expected to be reached upon supplement intake, the IC50 values of the present study point at possible flavonoid-drug and/or flavonoid-xenobiotic interactions especially regarding transport processes involved in toxicokinetics. © 2004 Elsevier Inc. All rights reserved.

Published
2004

29. Structural requirements for the flavonoid-mediated modulation of glutathione S-transferase P1-1 and GS-X pump activity in MCF7 breast cancer cells

Author

Nicole H.P. Cnubben, Peter J. van Bladeren, Jelmer J. van Zanden, Ivonne M.C.M. Rietjens, Heleen M. Wortelboer, Liesbeth Geraets, and TNO Voeding

Subjects
family, IC50, animal cell, Pharmacology, Toxicology, Biochemistry, quercetin, taxifolin, multidrug-resistance protein, glutathione transferase, toxicokinetics, S-(2,4-dinitrophenyl)glutathione, Tumor Cells, Cultured, heterocyclic compounds, eriodictyol, Biology Toxicology, multidrug resistance protein 1, multidrug resistance protein 2, flavanoid, chemistry.chemical_classification, food and beverages, Catechin, 1-chloro-2,4-dinitrobenzene, priority journal, Myricetin, plant polyphenols, hydroxyl group, 50% inhibition concentration, Multidrug resistance associated protein, Structure-Activity Relationship, catechin, Membrane Transport Modulators, GSH, Taxifolin, Humans, human, GST, luteolin, Toxicologie, VLAG, human cell, fungi, Membrane Transport Proteins, Eriodictyol, chemistry, Glutathione S-Transferase pi, P-gp, genetic transfection, Carrier Proteins, abc transporters, organic anion transporter, Flavonoid, myricetin, chemistry.chemical_compound, p-glycoprotein, lipophilicity, flavone derivative, chemical bond, enzyme inhibition, Glutathione Transferase, article, drug, 3',4' dihydroxyflavone, Glutathione, inhibition, Drug Resistance, Multiple, Multidrug Resistance-Associated Protein 2, CDNB, unclassified drug, enzyme activity, Galangin, Isoenzymes, GS-X, Multidrug Resistance-Associated Proteins, Quercetin, drug potency, MRP, Breast Neoplasms, Physiological Sciences, breast cancer, drug activity, DNP-SG, controlled study, gene, structure activity relation, Flavonoids, galanin, kaempferol, nonhuman, Glutathione conjugate, carbon, catechol derivative, IC 50, Biological Transport, morin, Glutathione S-transferase, cell strain MCF 7, Drug Resistance, Neoplasm, Luteolin
Abstract

The objective of this study was to investigate the structural requirements necessary for inhibition of glutathione S-transferase P1-1 (GSTP1-1) and GS-X pump (MRP1 and MRP2) activity by structurally related flavonoids, in GSTP1-1 transfected MCF7 cells (pMTG5). The results reveal that GSTP1-1 activity in MCF7 pMTG5 cells can be inhibited by some flavonoids. Especially galangin was able to inhibit almost all cellular GSTP1-1 activity upon exposure of the cells to a concentration of 25 muM. Other flavonoids like kaempferol, eriodictyol and quercetin showed a moderate GSTP1-1 inhibitory potential. For GSTP1-1 inhibition, no specific structural requirements necessary for potent inhibition could be defined. Most flavonoids appeared to be potent GS-X transport inhibitors with IC50 values ranging between 0.8 and 8 muM. Luteolin and quercetin were the strongest inhibitors with IC50 values of 0.8 and 1.3 muM, respectively. Flavonoids without a C2-C3 double bond like eriodictyol, taxifolin and catechin did not inhibit GS-X pump activity. The results of this study demonstrate that the structural features necessary for high potency GS-X pump inhibition by flavonoids are (1) the presence of hydroxyl groups, especially two of them generating the 3',4-catechol moiety; and (2) a planar molecule due to the presence of a C2-C3 double bond. Other factors, like lipophilicity and the total number of hydroxyl groups do not seem to be dominating the flavonoid-mediated GS-X pump inhibition. To identify the GS-X pump responsible for the DNP-SG efflux in MCF7 cells, the effects of three characteristic flavonoids quercetin, flavone and taxifolin on MRP1 and MRP2 activity were studied using transfected MDCKII cells. All three flavonoids as well as the typical MRP inhibitor (MK571) affected MRP1-mediated transport activity in a similar way as observed in the MCF7 cells. In addition, the most potent GS-X pump inhibitor in the MCF7 cells, quercetin, did not affect MRP2-mediated transport activity. These observations clearly indicate that the GS-X pump activity in the MCF7 cells is likely to be the result of flavonoid-mediated inhibition of MRP1 and not MRP2. Altogether, the present study reveals that a major site for flavonoid interaction with GSH-dependent toxicokinetics is the GS-X pump MRP1 rather than the conjugating GSTP1-1 activity itself. Of the flavonoids shown to be most active especially quercetin is frequently marketed in functional food supplements. Given the physiological levels expected to be reached upon supplement intake, the IC50 values of the present study point at possible flavonoid-drug and/or flavonoid-xenobiotic interactions especially regarding transport processes involved in toxicokinetics. (C) 2004 Elsevier Inc. All rights reserved.

Published
2003

30. Flavonoids as DNA topoisomerase antagonists and poisons: structure-activity relationships

Author

Constantinou, Andreas I., Mehta, R., Runyan, C., Rao, K., Vaughan, A., Moon, R., and Constantinou, Andreas I. [0000-0003-0365-1821]

Subjects
dna topoisomerase, Protein Conformation, dna drug complex, Pharmaceutical Science, etoposide, Support, U.S. Gov't, P.H.S, Analytical Chemistry, quercetin, chemistry.chemical_compound, myricetin, 4',6,7 trihydroxyisoflavone, Drug Discovery, 3 hydroxyflavone, 6 hydroxyflavone, flavone derivative, Topoisomerase II Inhibitors, heterocyclic compounds, phloretin, gyrase inhibitor, Electrophoresis, Agar Gel, biology, article, prunetin, food and beverages, galangin, enzyme activity, dna topoisomerase (atp hydrolysing), amsacrine, DNA Topoisomerases, Type I, Molecular Medicine, Myricetin, daidzein, Plasmids, 7 hydroxyflavone, isomerism, DNA damage, Stereochemistry, dna strand breakage, fisetin, Bioflavonoids, Topoisomerase-I Inhibitor, Hydroxylation, cancer chemotherapy, genistein, Structure-Activity Relationship, poison, catechin, Structure–activity relationship, controlled study, flavonoid, Pharmacology, structure activity relation, apigenin, Flavonoids, kaempferol, Topoisomerase, Organic Chemistry, teniposide, drug targeting, morin, DNA Topoisomerases, Type II, Complementary and alternative medicine, chemistry, biology.protein, dna cleavage, Topoisomerase-II Inhibitor, Topoisomerase I Inhibitors, Kaempferol, Fisetin, DNA Damage
Abstract

Selected flavonoids were tested for their ability to inhibit the catalytic activity of DNA topoisomerase (topo) I and II. Myricetin, quercetin, fisetin, and morin were found to inhibit both enzymes, while phloretin, kaempferol, and 4',6,7-trihydroxyisoflavone inhibited topo II without inhibiting topo I. Flavonoids demonstrating potent topo I and II inhibition required hydroxyl group substitution at the C-3, C-7, C-3', and C-4' positions and also required a keto group at C-4. Additional B-ring hydroxylation enhanced flavonoid topo I inhibitory action. A C-2,C-3 double bond was also required, but when the A ring is opened, the requirement for the double bond was eliminated. Genistein has been previously reported to stabilize the covalent topo II-DNA cleavage complex and thus function as a topo II poison. All flavonoids were tested for their ability to stabilize the cleavage complex between topo I or topo II and DNA. None of the agents stabilized the topo I-DNA cleavage complex, but prunetin, quercetin, kaempferol, and apigenin stabilized the topo II DNA-complex. Competition experiments have shown that genistein-induced topo II-mediated DNA cleavage can be inhibited by myricetin, suggesting that both types of inhibitors (antagonists and poisons) interact with the same functional domain of their target enzyme. These results are of use for the selection of flavonoids that can inhibit specific topoisomerases at specific stages of the topoisomerization reaction. © 1995, American Chemical Society. All rights reserved. 58 217 225 Tradenames: vm 26, bristol myers squibb, United States vp 16, bristol myers squibb, United States Manufacturers: aldrich, United States bristol myers squibb, United States gibco, United States sigma, United States Cited By :222

Published
1995

31. Crystal structure of 3-(4-meth-oxy-phen-yl)-2,3-di-hydro-1H-naphtho-[2,1-b]pyran-1-one.

Author

Vasanthi R, Reuben Jonathan D, Elizhlarasi KS, Revathi BK, and Usha G

Abstract

In the title compound, C20H16O3, the hydro-pyran ring adopts a distorted half-chair conformation with the methine C atom and the ring O atom displaced by -0.554 (2) and 0.158 (1) Å, respectively, from the plane of the other four atoms (r.m.s. deviation = 0.020 Å). Its mean plane (all atoms) is inclined to the naphthalene ring system at a dihedral angle of 11.67 (1)°. The dihedral angle between the napthalene ring system and the phenyl ring is 71.84 (1)°. In the crystal, no diectional inter-actions beyond van der Waals contacts could be identified.

Published
2015
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32. Crystal structure of (2S/2R,3S/3R)-3-hydroxy-2-phenyl-chroman-4-one.

Author

Belguedj R, Bouacida S, Merazig H, Chibani A, and Bouraiou A

Abstract

In the title mol-ecule, C15H12O3, the C atoms bearing the hy-droxy group and the phenyl ring are disordered over two sets of sites with refined occupancies of 0.573 (7) and 0.427 (7). There is also disorder of the phenyl ring but the hy-droxy group was refined as ordered. The dihedral angles between the benzene ring of the chromane ring system and the phenyl ring are 89.7 (2)° for the major component of disorder and 72.1 (3)° for the minor component. Both disorder components of the the di-hydro-pyran ring are in a half-chair conformation. In the crystal, mol-ecules are linked by pairs of O-H⋯O hydrogen bonds, forming inversion dimers with an R 2 (2)(10) graph-set motif. Weak C-H⋯π inter-actions link these dimers into ladders along [001].

Published
2015
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33. Chemistry in Eriocaulaceae

Author

Wagner Vilegas, Anne Lígia Dokkedal, Paulo Takeo Sano, Lourdes Campaner dos Santos, Universidade Estadual Paulista (Unesp), and Universidade de São Paulo (USP)

Subjects
conformation, Models, Molecular, Xanthones, Molecular Conformation, Pantropical, chemistry, General Biochemistry, Genetics and Molecular Biology, Molecular conformation, Structure-Activity Relationship, Eriocaulaceae, Botany, flavone derivative, flavonoid, xanthone derivative, structure activity relation, Flavonoids, biology, isolation and purification, Chemistry, Chemical data, Flavones, biology.organism_classification, Chemotaxonomy, classification, xanthone, chemical structure, Taxonomy (biology)
Abstract

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:22:49Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:38:11Z : No. of bitstreams: 1 2-s2.0-49649127665.pdf: 191238 bytes, checksum: 1bc56fd6d4260980c0f9aecf463776e6 (MD5) Made available in DSpace on 2014-05-27T11:22:49Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-03-01 Eriocaulaceae is a pantropical family that comprises about 1100 species distributed in 11 genera. The infrafamilial relationships are still unsatisfactorily resolved, because of the tiny flowers and generalized morphology, which makes the taxonomy very difficult. Flavonoid and naphthopyranone profiles have proved to be important in order to contribute to the alignment of genera into the family. We here present a survey of the chemical data of Eriocaulaceae with a discussion about their contribution to the taxonomy of Eriocaulaceae. © 2008 Verlag der Zeitschrift für Naturforschung. Departamento de Ciências Biológicas Faculdade de Ciências UNESP, C.P. 473, 17033-360 Bauru, SP Departamento de Química Orgânica Instituto de Química de Araraquara UNESP, C.P. 355, 14801-970 Araraquara, SP Departamento de Botânica Instituto de Biociências Universidade de São Paulo, C.P. 11461, 05427-970 São Paulo, SP Departamento de Ciências Biológicas Faculdade de Ciências UNESP, C.P. 473, 17033-360 Bauru, SP Departamento de Química Orgânica Instituto de Química de Araraquara UNESP, C.P. 355, 14801-970 Araraquara, SP

34. Separation of flavonoids and naphthopyrones from four Brazilian Paepalanthus species by droplet countercurrent chromatography

Author

Santos, Lourdes Campaner Dos, Andrade, F. D. P., Vasconcelos, E. C., Coelho, R. G., Dokkedal, A. L., Garcia, A. C. L., Sano, P. T., Wagner Vilegas, and Universidade Estadual Paulista (Unesp)

Subjects
Flavonoids, column chromatography, drug isolation, data analysis, species difference, 9 o beta dextro glucopyranosylpaepalantine, naphthopyrone, Paepalanthus extract, plant, Paepalanthus, unclassified drug, spectrometry, 9 o beta dextro glucopyranosyl(1-6)allopyranosylpaepalantine, counter current chromatography, Eriocaulaceae, flavone derivative, DCCC, flavonoid, Naphthopyrones
Abstract

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:19:50Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:39:33Z : No. of bitstreams: 1 2-s2.0-0033298456.pdf: 742023 bytes, checksum: cd347e4e5e0c0c14bdbee9e1b0b725a1 (MD5) Made available in DSpace on 2014-05-27T11:19:50Z (GMT). No. of bitstreams: 0 Previous issue date: 1999-12-01 A general procedure was developed for the simultaneous separation of flavonoids and naphthopyrones from the polar extracts of the capitula from Brazilian everlasting plants is described. The ethanolic extracts of several species from the Paepalanthus genus (Eriocaulaceae) were fractionated by droplet countercurrent chromatography followed by column chromatography on pvp and sephadex LH-20. The isolated compounds were identified by spectrometric analysis and comparison with literature data. This approach led to the isolation of 9-O-β-D-glucopyranosylpaepalantine (1), 9-O-β-D-glucopyranosyl (1→6)allopyranosylpaepalantine (2), along with the flavonoids 6-methoxykaempferol (3), 3-O-β-D-glucopyranosyl-6-methoxykaempferol (4), patuletin (5), 3-Oβ-D-rutinosylpatuletin (6), 7-O-β-D-glucopyranosylquercetagetin (7), 5,7,4'-trihydroxy-6,3'-dimethoxyflavone (8) and 5,7,4'-trihydroxy-6,3'-dimethoxyflavonol (9). Departamento de Quimica Organica UNESP, C.P. 355, 14800-900 - Araraquara - SP Departamento de Quimica Organica UNESP, C.P. 355, 14800-900 - Araraquara - SP

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