A NEW AND EFFICIENT SYNTHESIS OF 3-IODO DERIVATIVES OF FLAVONES, THIOFLAVONES AND THIOCHROMONES

The title compounds are prepared in good yields by iodination of the corresponding flavones, thioflavones and thiochromones respectively using I_2-CAN(ceric ammonium nitrate) system. The compounds thus prepared are potentially useful precursors for the synthesis of C-3 linked binuclear compounds.

Antioxidations and Their Correlations with Total Flavones and Anthocyanin Contents in Different Black Rice Varieties

The antioxidations and their correlations with total flavones and anthocyanin contents in different black rice varieties were studied. The results indicated that the great differences in total antioxidant capacity （TAC）, scavenging free radical capacity （SFRC）, total flavones and anthocyanin contents existed among 242 black rice varieties. Comparisons of TAC, SFRC, total flavones and anthocyanin contents of different black rice types showed that the differences between black rice and white rice, indica one and japonica one, and nonglutinous one and glutinous one were significant at 0.01 levels, respectively. This showed that the TAC, SFRC, total flavones and anthocyanin contents of japonica type were higher than those of indica one, and nonglutinous type were higher than glutinous one. According to the fast clustering procedure, 242 black rice varieties could be clustered into 10 clusters, 184 indica rice varieties into 10 clusters, and 58 japonica rice varieties into 6 clusters. Most significant （P〈0.01） correlations existed between TAC and total flavones and anthocyanin contents, and between SFRC and total flavones and anthocyanin contents of black rice, respectively. This showed that the antioxidation of black rice was closely correlated with its active compositions of flavones and anthocyanin.

ANTAGONISM OF TOTAL FLAVONES OF GYNOSTEMMA PENTAPHYLLUM (THUNB) MAK TO ANIMAL EXPERIMENTAL ARRHYTHMIA

The action of total flavones of Gynostemma pentaphyllum (Thunb) Mak (TFG) 60 mg/kg i.v. could prevent arrhythmias induced by drugs and myocardial ischemia were investigated. In anesthetized rats and guinea pigs. The results showed that in TFG group the duration of ventricular tachycardia (VT) induced by aconitine in rats was shortened (P<0 01) and the incidence of ventricular fibrillation (VF) and the mortality were decreased (P<0 01) respectively. The arrhythmias induced by i.v. BaCl 2 4 mg/kg in rats were immediately recovered to a normal sinus rhythm and VT induced by i.v. CaCl 2 130 mg/kg in rats was decreased by TFG i.v. TFG i.v. elevated the doses of i.v. strophanthin G to induce ectopic beats (EB), VT, VF and cardiac arrest (CA) in guinea pigs by 89%, 58%, 27%, and 28% (P<0 01) respectively. The incidence of VF induced by coronary artery ligation in rats was decreased (P<0 01), duration of EB, duraton of VT and VF decreased to 45%, 42% and 0% of the NS group respectively. The results suggest that TFG in dosage of 60 mg/kg might be useful for the prevention of VT and VF.

In Vitro Anti-viral Activities and Structureactivity Relationship Studies of Flavones and Dihydroflavone Derivatives as Influenza Virus Potential Neuraminidase Inhibitors

From the bioassay tests, 14 neuraminidase inhibitors （NIs） flavones and dihydroflavones derivatives from natural plants displayed different degree of inhibitory activities. Further- more, compounds No. 8 and 14 showed good inhibitory activity against influenza A virus with IC50 = 835.4 and 860.6 μg/mL. Then, to investigate interactions between NIs and neuraminidase （NA）, molecular docking was performed. Docking results indicated that Arg118, Asp151, Arg292 and Arg371 were the key residues in the active pocket of 2ht8. Main influencing factors of interactions between NIs and NA were hydrogen bond and electrostatic, then hydrophobic factor. Moreover, experimental activities of NIs were consistent with total scores of the docking. In order to understand the chemical-biological interactions governing their activities toward NA, QSAR models of 14 NIs were developed. The obtained HQSAR （hologram quantitative structure activity relationship）, PLS （partial least squares） and SRA （stepwise regression analysis） models were robust and had good exterior predictive capabilities. Moreover, squared multiple correlation coefficients （R2） and squared cross-validated correlation coefficients （Q2） of HQSAR and PLS models based on descriptors by Gaussian and Sarchitect were 0.832 and 0.721, 0.925 and 0.688, 0.892 and 0.692, respectively. R2 and SE （standard error） of SRA model based on descriptors by Gaussian were 0.922 and 0.072. Therefore, these models may be further used to design and evaluate the bioactivity of new compounds.

Development of mild and efficient method for synthesis of substituted flavones using oxalic acid catalyst

Oxalic acid has been used as a catalyst for intramolecular cyclisation of 2-hydroxychalcones to form flavones in good yields. The efficiency of the catalyst was proved with a variety of substrates ranging from electron-deficient to electron-rich aryl aldehydes and 2-hydroxychalcone.

Immunoregulatory Effects of Sanguis Draconis Flavones on Mouse Spleen Lymphocytes

[Objectives] This study aimed to study the effects of Sanguis Draconis flavones( SDF) on the immune regulation of mouse spleen lymphocytes. [Methods]A total of 60 BALB/c male mice were evenly and randomly divided into normal control group,model group,positive group,and high,middle and low-dose SDF groups. The mice in the model group were injected intraperitoneally with cyclophosphamide to establish mouse immunosuppressive model. The mice in the other groups were intragastrically administered at the respective doses,and the body weight was weighed once a week during the administration period. After 30 d of administration,the thymus and spleen indexes,the spleen lymphocyte proliferation ability,the NK cell activity,and the IL-2,IL-4 and INF-γ contents in the culture supernatant were measured. [Results]SDF could significantly increase the thymus and spleen indexes and improve the spleen lymphocyte proliferation ability and NK cell activity of the mice,as well as increasing the IL-2 and INF-γ contents and reducing the IL-4 content in spleen lymphocyte suspension culture. [Conclusions] SDF have good immunoregulatory effect.

Protective Effect of GRK2 and Effect of Sanguis Draconis Flavones on Focal Cerebral Ischemia-Reperfusion Injury in Rats

[Objectives] To explore the protective effect of Sanguis Draconis flavones (SDF) on rat focal cerebral ischemia-reperfusion injury (CIRI) models established by middle cerebral artery occlusion (MCAO).[Methods] A total of 60 healthy adult male Sprague-Dawley rats were selected. They were evenly and randomly divided into sham group, model group, edaravone group (12 mg/kg) and SDF group (360 mg/kg), and administered intragastrically and intraperitoneally. The middle cerebral artery of each rat was blocked by suture-occluded method to establish a CIRI model. After ischemia for 2 h and reperfusion for 48 h, the pathological injury on the ischemic side was observed by HE staining;the neuron and myelin sheath structure was observed by transmission electron microscopy;the expression of G protein-coupled receptor kinase 2 (GRK2) was preserved by immunohistochemistry;and the transfer of GRK2 was detected by western-blot.[Results] After 48 h of CIRI, the nuclei of the penumbral cortical neurons shrank, the chromatin was unevenly distributed, the nuclear membrane was dissolved and the mitochondria in the cytoplasm were swollen and vacuolated. The myelin layer was disordered. With this change, the distribution of GRK2 subcellular cells in the penumbra of the injured lateral cortex transferred from the cytoplasm to the membrane. SDF can effectively restore neuronal and myelin sheath structural damage and reduce the functional (membrane coupling) expression of GRK2.[Conclusions] GRK2 may be an effective target for SDF to protect the impaired blood-brain barrier (BBB) in CIRI.

Research Progress of Total Flavones in Marchantia convoluta

According to the literature retrieval,the composition,detection method,preparation method and product development of total flavones in Marchantia convoluta were reviewed and prospected. This paper will provide a theoretical basis for further study and product development of total flavones in M. convoluta.

Structure of Flavones and Flavonols. Part II: Role of Position on the O-H Bond Dissociation Enthalpy

The enthalpies of bond dissociations of the hydroxyl groups, the energy of the highest occupied molecular orbitals and the corresponding radicals spin densities of all possible ten isomeric mono-hydroxyl flavones are calculated by means of 3-parameter Becke, Lee, Yang and Parr functional. The structural factors affecting these descriptors of radical-scavenging activity are outlined. The results obtained show that the hydroxyl groups in ring A and C are more involved in the process of a radical-capturing than recently believed.

The neuroprotective efets of total flavones of Dracoce phalum moldavica L.on Parkinson's disease model in mouse

It was found that the extract of total flavones from Dracoce phalum moldavica L.(TFD)could exert neuroprotective effect on moase Parkinson's disease(PD)model,but the underlying mechanisms remained unclear.The aim of this study was to detect the mechanisms of TFD neuroprotective effect on PD mice.The PD model was established by injection with MPTP to mice.Using behavioral experiment and ELISA test as well as immunohistochemistry and Western blot analysis,the following parameters were examined:①the falling latency and climbing time,②the content of serum MDA as well as activities of SOD and GSH-Px,③the count of dopaminergic neurons with expression of TH in the substantia nigra of model mice,and④the expression levels of TH,caspase-3,Bcl-2 and Bax in the midbrain tissue.

A 180-Day Subchronic Oral Toxicity Study of Total Flavones of <i>E. leptorrhizum</i>Stearn in Rats

A subchronic oral toxicity was conducted to evaluate the safety of total flavones of E. leptorrhizum Stearn in Sprague-Dawley rats. The test article was administered once daily by gavage in male and female rats at dose levels of 24, 48, and 96 mg/kg body weight/day for 180 days. 90 and 180 days after administration, ten and tweedy animals (each half of male and female) of each group were tested. 28 days after withdrawal, five male and female rats were tested. There were no significant toxicological changes shown in daily clinical signs, body weight, food consumption, hematology parameters, blood biochemistry, organ weights and histopathological examination except leukocyte differential count. It was concluded that the no-observed-effect level (NOEL) for total flavones of E. leptorrhizum Stearn was >96 mg/kg in SD rats.

A Study on the Whitening Efficacy of Flavones in Lotus Leaf

Taking lotus flavones as the research object, cytotoxicity was evaluated by MTT test, inhibitory effects onthe activity of tyrosinase was studied, and DPPH scavenging experiments were carried out. Lotus flavoneswere used in a formula of skin cream and facial whitening effects were examined. Results shows that lotusflavones are exhibited no cytotoxicity at a concentration equal or less than 1%, and it can decrease the activityof tyrosinase at a concentration between 0.02%~0.30%. Lotus flavones can scavenge DPPH radical. The skincream containing lotus flavones declines facial melanin content. Lotus flavones have good biological safety andare suitable in cosmetics as whitening agents.

Synthesis of A New Group of Flavones Containing Crown Ether Moiety

Flavones are main components of natural occurring flavonoils. It is well documented in the literatures that flavones are known to exhibit a wide variety of biological and pharmaceutical activities. Many of them have been used therapentically for the treatments of symptoms of chronic venous insufficiency, of varicose veins, of conditions and of diabetic retinopathy, etc.. Some flavones have

Immunological Effects of Total Flavones from Leaves of Choerospondias axillaris on Mice

ObjectiveTo investigate the effect of total flavones from the leaves of Choerospondias axillaris (TFLCA) on the immune function of normal mice and to provide the experimental basis for the reasonable application of C. axillaris.MethodsThe carbon clearance method, cutaneous delayed hypersensitivity reaction method, serum hemolysin method, and index of immune organs were used to study the effect of TFLCA on the immune function of mice.ResultsTFLCA could enhance the phagocytic function of mononuclear macrophage and the cutaneous delayed hypersensitivity reaction of mice, and increase the content of hemolysin antibody and the thymus index in mice.ConclusionTFLCA could improve the celiac macrophage activity and specific immunity of mice, and TFLCA, consisting with the total flavones of Choerospondiatis Fructus (TFCF), has the effect on the immune function of mice. So both TFLCA and TFCF have the regulatory effects on the immune function of mice.

Recent advances in the diversification of chromones and flavones by direct C-H bond activation or functionalization

Chromone and flavone are both central backbones of natural products and clinical medicines.Synthesis of diversely functionalized chromones and flavones constitutes significant research contents of the modern synthetic science because abundant molecular libraries of such types are crucial in providing candidate compounds for the discovery of new pharmaceuticals and functional materials.The direct C—H bond activation or functionalization on these heterocyclic backbones provides highly powerful tools for the rapid accesses to densely functionalized chromone and flavone derivatives.Considering the importance of the functionalized chromone and flavone compounds as well as the notable advances in the synthesis of such products by direct C—H activation or functionalization,we review herein the research advances in the C—H bond activation and functionalization reactions of chro mone and flavones,in hope of showing the current states and promise of the research domain.

Natural variation of GmFNSII-2 contributes to drought resistance by modulating enzyme activity in soybean

As an essential crop that provides vegetable oil and protein,soybean(Glycine max(L.)Merr.)is widely planted all over the world.However,the scarcity of water resources worldwide has seriously impacted on the quality and yield of soybean.To address this,exploring excellent genes for improving drought resistance in soybean is crucial.In this study,we identified natural variations of GmFNSII-2(flavone synthase II)significantly affect the drought resistance of soybeans.Through sequence analysis of GmFNSII-2 in 632 cultivated and 44 wild soybeans nine haplotypes were identified.The full-length allele GmFNSII-2^(C),but not the truncated allele GmFNSII-2^(A) possessing a nonsense nucleotide variation,increased enzyme activity.Further research found that GmDREB3,known to increase soybean drought resistance,bound to the promoter region of GmFNSII-2^(C).GmDREB3 positively regulated the expression of GmFNSII-2^(C),increased flavone synthase abundance and improved the drought resistance.Furthermore,a singlebase mutation in the GmFNSII-2^(C) promoter generated an additional drought response element(CCCCT),which had stronger interaction strength with GmDREB3 and increased its transcriptional activity under drought conditions.The frequency of drought-resistant soybean varieties with Hap 1(Pro:GmFNSII-2^(C))has increased,suggesting that this haplotype may be selected during soybean breeding.In summary,GmFNSII-2^(C) could be used for molecular breeding of drought-tolerant soybean.

Effects of ginkgo flavone aglycone on atherosclerosis based on network pharmacology,molecular docking,and in vitro experiments

Background:Ginkgo flavone aglycones(GA),a Ginkgo(Ginkgo biloba)extract,has been proven to have good biological activity in atherosclerosis(AS)treatment.Moreover,its active compounds and the corresponding mechanism for the treatment of AS remain unclear.Methods:To evaluate and identify the potential pharmacological mechanisms of GA in AS treatment,the program Cytoscape was used to generate network mappings of the GA-AS-potential target gene.GO and KEGG enrichment analyses were performed to further investigate the potential mechanism of AS and the pharmacological properties of GA.A molecular docking approach was utilized to determine the GA components that interact with Akt.In vitro experiments were carried out to identify the anti-atherosclerotic effects of GA by targeting Akt.Results:Network pharmacological research determined that the active components of GA(quercetin,kaempferol,and isorhamnetin)correlated with AS target genes such as AKT1,EGFR,SRC,ESR1,PTGS2,MMP9,KDR,GSK3B,APP,and MMP2,respectively.GO enrichment and KEGG analysis showed that PI3K-Akt signaling may play an important role in GA treatment.Molecular docking experiments indicated that quercetin,kaempferol,and isorhamnetin integrate into the binding pockets of the most potentially beneficial GA-AS target protein(Akt).Consequently,cell experiments were conducted to support the anti-atherosclerotic activity of GA on AS by inhibiting the phosphorylation of AKT1 and its downstream signaling molecules,which regulated the proliferation of HASMCs.Conclusion:Our results detailed GA's active ingredients,potential targets,and molecular basis against AS.GA may exert anti-atherosclerotic effects by suppressing Akt phosphorylation and inhibiting the proliferation of HASMCs.It also proposed a viable approach to determining the scientific foundation and therapeutic mechanism of Chinese herbal medicine extracts in disease therapy.

Nobiletin and tangeretin(citrus polymethoxyflavones): an overview on their chemistry, pharmacology and cytotoxic activities against breast cancer

The fruit peel of Citrus species(Chenpi),particularly those of mandarin oranges,is a useful source of food and medicine in China.Flavonoids from the citrus fruit peel are mainly polymethoxyflavones(PMFs),of which nobiletin and tangeretin are the most abundant components.In the present review,we summarized the cytotoxic activities of these two PMFs to breast cancer cells.Studies have reported that these two compounds inhibit the growth of breast cancer cells by inducing apoptosis,cytostatic cell death and cell cycle arrest,or by inhibiting cell proliferation,metastasis and tumour angiogenesis,depending on the molecular subtypes of breast cancer.In vitro and in vivo cytotoxic activities involve different molecular targets and signalling pathways.Analyses on the structure-activity relationship(SAR)of nobiletin and tangeretin have shown that the presence of a methoxy group at C8 and a hydroxyl group at C3 or C5 are essential for anti-proliferative activity.Some future perspectives and research needs are suggested.Sources of information are from Pub Med,Pub Med Central,Science Direct,Google Scholar,J-Stage,Pub Chem and CNKI using keyword search.

Two CYP82D Enzymes Function as Flavone Hydroxylases in the Biosynthesis of Root-Specific 4＇-Deoxyflavones in Scutellaria baicalensis

Baicalein, wogonin, and their glycosides are major bioactive compounds found in the medicinal plant Scutellaria baicalensis Georgi. These flavones can induce apoptosis in a variety of cancer cell lines but have no effect on normal cells. Furthermore, they have many additional benefits for human health, such as antioxidant, antiviral, and liver-protective properties. Here, we report the isolation and characterization of two CYP450 enzymes, SbCYP82D1.1 and SbCYP82D2, which function as the flavone 6-hydroxylase （F6H） and flavone 8-hydroxylase （F8H）, respectively, in S. baicalensis. SbCYP82D1.1 has broad substrate speci- ficity for flavones such as chrysin and apigenin and is responsible for biosynthesis of baicalein and scutel- larein in roots and aerial parts of S. baicalensis, respectively. When the expression of SbCYP82D1.1 is knocked down, baicalin and baicalein levels are reduced significantly while chrysin glycosides accumulate in hairy roots. SbCYP82D2 is an F8H with high substrate specificity, accepting only chrysin as its substrate to produce norwogonin, although minor 6-hydroxylation activity can also be detected. Phylogenetic analysis suggested that SbCYP82D2 might have evolved from SbCYP82D1.1 via gene duplication followed by neofunctionalization, whereby the ancestral F6H activity is partially retained in the derived SbCYP82D2.