Gotowa bibliografia na temat „2'.3-Dihydroxyflavone”

In the present paper, we are interested, for the first time, to separate and identify two glycosyl the flavones from Sedum villosum L, family Crassulaceae collected in the flowering phase in Lakhdar Oued, village of Tlemcen (Algeria). The crude methanolic extract of the flowers part was fractionated on column chromatography, and eluted with dichloromethane/methanol each time with increasing polarity of methanol; 24 fractions were separated. One of these fractions named F16 showed more antioxidant activity to scavenge DPPH free radical with percentage inhibition of 94.849 %. F16 was separated by thin-layer chromatography (TLC) to give 10 compounds. We were chosen the sub-fractions F16.8, which has antioxidative activity of 77.02 %, provided two major molecules of glycosyl the flavones, analysed by ultra-highperformance liquid chromatography coupled to mass spectrometry (UHPLC-DAD-HRSM). Compound 1 was identified as 7, 3'-dihydroxyflavone-5-O-dihexosyl-4'-O-deoxyhexose and compound 2 was 7, 3'-dihydroxyflavone-5-O-hexose- 4'-O-deoxyhexose.

Three additional flavonoids such as 5,7,4?-trihydroxy-3,8,3?-trimethoxy flavonol (1), 5,7-dihydroxyflavone (chrysin, 2) and 5,6,7-trihydroxyflavone (baicalein, 3) were obtained from the methanol extract of whole plant of Polygonum viscosum. The structure of the isolated compounds was established exclusively by ultraviolet (UV) spectroscopy, mass spectrometry (MS) and a series of Nuclear Magnetic Resonance (NMR) analysis.Dhaka Univ. J. Pharm. Sci. 15(1): 27-30, 2016 (June)

Amyloid-β and α-synuclein aggregation into amyloid fibrils is linked to the onset and progression of Alzheimer’s and Parkinson’s diseases. While there are only a few disease-modifying drugs, it is essential to search for new, more effective ways to encounter these neurodegenerative diseases. Multiple research articles have shown that the autoxidation of flavone is a critical factor for activating the inhibitory potential against the protein aggregation. Despite this, the structure of the newly-formed inhibitors is unknown. In this research, we examined the autoxidation products of 2′,3′-dihydroxyflavone that were previously shown to possess one of the most prominent inhibitory effects against amyloid-β aggregation. Their analysis using HPLC suggested the formation of polymeric molecules that were isolated using a 3 kDa cut-off. These polymeric structures were indicated as the most potent inhibitors based on protein aggregation kinetics and AFM studies. This revelation was confirmed using MALDI-TOF and NMR. We also show that active molecules have a tendency to reduce the Amyloid-β and α-synuclein aggregates toxicity to SH-SY5Y cells.

Introduction: Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by progressive degeneration of both upper and lower motor neurons, resulting in paralysis and eventually leads to death from respiratory failure typically within 3 to 5 years of symptom onset. The aim of this work was to predict the pharmacokinetics and identify unique protein targets that are associated with potential anti-ALS phytochemicals and FDA-approved drugs, by in silico approaches. Materials and methods: Standard computational tools (webserver and software) were used, and the methods used are clustering analysis, pharmacokinetics and molecular target predictions, and molecular docking simulation. Results and discussion: The results show that riluzole, β-asarone, cryptotanshinone, harmine and 7,8-dihydroxyflavone have similar pharmacokinetics properties. Riluzole and harmine show 95% probability of target on norepinephrine transporter. Huperzine-A and cryptotanshinone show 100% probability of target on acetylcholinesterase. 7,8-dihydroxyflavone shows 35% probability of target on several carbonic anhydrases, 40% probability of target on CYP19A1, and 100% probability of target on inhibitor of nuclear factor kappa B kinase beta subunit and neurotrophic tyrosine kinase receptor type 2, respectively. Harmine also shows 95% probability of target on dual specificity tyrosine-phosphorylation-regulated kinases, threonine-protein kinases (haspin and PIM3), adrenergic receptors, cyclin-dependent kinases (CDK5 and CDK9), monoamine oxidase A, casein kinase I delta, serotonin receptors, dual specificity protein kinases (CLK1, CLK2, and CLK4), and nischarin, respectively. Also, the results of gene expression network show possible involvement of CDK1, CDK2, CDK4, ERK1, ERK2 and MAPK14 signaling pathways. This study shows that riluzole and harmine have closely similar physicochemical and pharmacokinetics properties as well as molecular targets, such as norepinephrine transporter (SLC6A2). Harmine, huperzine-A and cryptotanshinone could modulate acetylcholinesterase (AChE), which is involved in ALS-pathogenesis. The impact of 7,8-dihydroxyflavone on several carbonic anhydrases (CA) I, II, VII, IX, XII, and XIV, as well as CYP19A1, could help in remediating the respiratory failure associated with ALS. Conclusion: Overall, harmine is found to be superior to riluzole, and the combination of harmine with 7,8-dihydroxyflavone can provide more effective treatment for ALS than the current regime. Further work is needed to validate the predicted therapeutic targets of harmine identified in this study on ALS model or clinical trials, using in silico, in vitro and in vivo techniques. Graphical abstract:

Ethnopharmacological Relevance. Dragon’s blood (DB) is a widely used traditional Chinese medicine that has many pharmacological effects, including antiplatelet aggregation, promoting epidermal growth, and anti-inflammatory and antioxidant activities. The main component of Longxuetongluo capsule and Dragon’s blood dropping pills is DB’s standard phenolic extract, which was used for ischemic stroke prognosis in China. Aim of Study. To dissect the molecular mechanisms of Dragon’s blood (DB) in improving ischemic stroke prognosis. Materials and Methods. (1) Based on system-pharmacology platform, the potential active compounds of DB are screened out according to ADME. (2) The ischemic stroke-related targets are predicted by utilizing these active compounds as probes, mapping the targets to the CTD database to establish a molecular-target-disease network. (3) To analyze the mechanism of DB treatment for the prognosis of ischemic stroke, we used the Metascape and DAVID databases to construct “ischemic stroke pathways”. (4) PC12 cells were used to explore the protective effect of loureirin B on oxygen-glucose deprivation/reperfusion (OGD/R) injury, and BV-2 cells were used to determine the anti-inflammation effect of 4′,7-dihydroxyflavone. Results. Finally, we obtained 38 active compounds and 58 stroke-related targets. Network and pathway analysis indicate that DB is effective in the treatment of ischemic stroke by enhancing cell survival and inhibiting inflammatory and antiplatelet activation. In in vitro experiments, the main component loureirin B promoted the expression of HO-1 and Bcl-2 via positive regulation of PI3K/AKT/CREB and Nrf2 signaling pathways in PC12 cells against OGD/R damage. And the anti-inflammatory activity of 4′,7-dihydroxyflavone was related to the inhibition of COX-2, TNF-α, and IL-6 in LPS-induced BV-2 cells. Conclusions. In our study, the results illustrated that DB in improving ischemic stroke prognosis may involve enhancing cell survival and antioxidant, anti-inflammation, and antiplatelet activities.

Antitubercular bioassay-guided fractionation of the dichloromethane extracts of the above-ground biomass and roots of Quinchamalium majus led to the identification of six known constituents, betulinic acid (1), daucosterol (2), 5,7-dihydroxyflavone (3), oleanolic acid (4), (D)-2S-pinocembrin (5), and ursolic acid (6), for the first time in this species. Their chemical structures were determined on the basis of spectroscopic evidence and chemical transformation methods. All of these compounds along with additional 11 analogues were evaluated for their antitubercular potential against Mycobacterium tuberculosis in a microplate alamar blue assay, and the primary structure-activity relationships (SARs) for 4 and 6 were discussed. In addition, all the isolates were tested for cytotoxicity against African green monkey Vero cells in order to evaluate for their selectivity potential.

Doxorubicin-induced cardiotoxicity is the leading cause of morbidity and mortality among cancer survivors. The present study aimed to investigate the ameliorative effect of 5, 7-dihydroxyflavone (chrysin) against doxorubicin-induced cardiotoxicity in Wistar rats. Thirty-five adult male Wistar albino rats were randomly allocated into seven groups (n = 5 each) which consisted of normal control (group 1) receiving phosphate buffer saline (0.4 ml), positive control (Group 2) received 2mg\kg of doxorubicin (DOX) through an intraperitoneal route once weekly for 21 days, chrysin low dose and chrysin high dose (Group 3 and 4) received oral administration of chrysin 50&100mg/kg for 21 days, chrysin low dose and DOX, chrysin medium dose and DOX and chrysin high dose and DOX(group 5, 6, and 7) received 2mg/kg of DOX once weekly with 50, 100 and 150mg/kg of chrysin for 21 days. Significant elevations in cardiac troponin I (cTnI) and histological lesions, which corresponded with oxidative stress, inflammation, apoptotic indicators, and cardiotoxicity when compared to controls, were indicative of DOX-induced cardiotoxicity. Malondialdehyde (MDA), a sign of oxidative stress, SOD, CPK (creatinine phosphokinase), TBARS (thiobarbituric acid reactive substance), and CAT (catalase) were also elevated in the DOX group. The DOX group also had increased levels of cardiac inflammatory markers, including as interleukin-1 (IL-1), interleukin-6 (IL-6), and the apoptotic marker caspase-3. 5, 7-dihydroxyflavone (chrysin) significantly mitigated, but did not entirely reverse, the cardiotoxicity caused by DOX by reducing the histopathological scores of cardiomyopathies and lowering cTnI in comparison to the DOX group. Additionally, chrysin reduced MDA to substantially similar levels as the control. Following chrysin administration, significant decreases in IL-1, IL-6, and caspase-3 were also seen in comparison to the DOX-only group. All things considered, these findings point to chrysin's protective action against DOX-induced cardiotoxicity, which may have been rendered possible by oxidative stress, inflammatory, and apoptotic suppression.

Ce manuscrit présente les résultats d'une étude expérimentale et théorique de deux systèmes moléculaires d'intérêt environnemental : la 2',3-dihydroxyflavone (2'3HF) et les hydrocarbures aromatiques polycycliques (HAP). Ces systèmes ont été étudiés par une combinaison de techniques de spectroscopies électroniques (absorption et fluorescence) et de calculs de chimie quantique (DFT et TD-DFT). Dans une première partie de cette thèse, il est montré que la 2'3HF présente des propriétés acido-basiques singulières par rapport aux autres flavonols. La diminution de plusieurs unités de la valeur du pKa est attribuée à la présence d'un réseau de liaisons hydrogènes. A l'état-excité, un transfert de proton intramoléculaire est à l'origine d'une fluorescence duale. Une bande d'émission supplémentaire, semblant provenir d'une forme tautomère perturbée par interaction avec le solvant, a été mise en évidence. Enfin, une étude exhaustive des complexes de Ca(II), Mn(II) et Zn(II) a montré la formation de chélates avec la fonction α-hydroxycétone. Dans la deuxième partie, trois hypothèses structurales pour expliquer l'observation expérimentale de fluorescence induite par laser (LIF) dans le visible ont été explorées. Une étude sur les dimères de van der Waals (vdW) des HAPs a permis de mieux comprendre la nature de l'interaction entre monomères et de mettre en évidence la difficulté de modéliser ces systèmes, cependant, les transitions électroniques calculées suggèrent que ces espèces ne peuvent pas être responsables des signaux de LIF. Ensuite, une étude identique de HAP liés par ponts aliphatiques a montré des résultats très similaires aux dimères de vdW, excluant leur implication dans la fluorescence observée. Enfin, l'hypothèse de l'émission provenant de radicaux de HAPs a été explorée. Cette dernière est très prometteuse et ouvre la voie à des études expérimentales et théoriques ultérieures
This manuscript reports the results of an experimental and theoretical study of two molecular systems of environmental interest: 2',3-dihydroxyflavone (2'3HF) and polycyclic aromatic hydrocarbons (PAH). These systems were studied by a combination of electronic spectroscopic techniques (absorption and fluorescence) and quantum chemical calculations (DFT and TD-DFT). In the first part of this thesis, it is shown that 2'3HF has singular acid-base properties compared to other flavonols. The decrease of the pKa by several units is attributed to the presence of a hydrogen-bond network. In the excited state, an intramolecular proton transfer causes a dual fluorescence. An additional emission band, seemingly originating from a tautomeric form perturbed by interaction with the solvent, was revealed. Finally, an exhaustive study of the Ca(II), Mn(II) and Zn(II) complexes showed the formation of chelates with the α-hydroxyketone function. In the second part, three structural hypotheses to explain the experimental observation of visible-range laser-induced fluorescence (LIF) were explored. A study of van der Waals (vdW) dimers of PAHs provided insights into the nature of the monomer interaction and highlighted the difficulty of modelling these systems. However, the calculated electronic transitions suggest that these species cannot be responsible for the LIF signals. Secondly, an identical study of aliphatically bridged PAHs showed very similar results to vdW dimers, ruling out their involvement in the observed fluorescence. Finally, the hypothesis of emission from PAH radicals was explored. The latter is very promising and opens the way for further experimental and theoretical studies