- Ruthenium(II) trithiacyclononane complexes of 7,3′,4′-trihydroxyflavone, chrysin and tectochrysin: Synthesis, characterisation, and cytotoxic evaluation
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This study describes a simple, two-step method for obtaining ruthenium(II) trithiacyclononane ([9]aneS3) flavonate complexes in yields ranging from 23% to 34%. With 7,3′,4′-trihydroxyflavone (thflv), a neutral complex, [Ru(II)([9]aneS3)(DMSO)(thflv)] (1), is formed by coordination at the catechol group. With chrysin (chrys) and tectochrysin (tchrys), Ru(II) binds to the chromenone fragment to form cationic complexes that are isolated as [Ru(II)([9]aneS3)(chrys)(DMSO)]Cl (2) and [Ru(II)([9]aneS3)(DMSO)(tchrys)]Cl (3). The structure of the complexes is characterised by FT-IR, NMR and ESI+-MS. Furthermore, the flavones and the corresponding complexes, 1–3, were investigated regarding their in vitro cytotoxic activity towards four different human tumour cell lines, PC-3 (prostate), MG-63 (osteosarcoma), MCF-7 and MDA-MB-231 (both breast adenocarcinoma).
- Marques, Joana,Silva, Artur M.S.,Marques, Maria Paula M.,Braga, Susana S.
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Read Online
- A novel one-pot synthesis of flavones
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In this paper, a one-pot facile route for the BiCl3/RuCl3-mediated synthesis of functionalized flavones is described, including: (i) intermolecularortho-acylation of substituted phenols with cinnamoyl chlorides, and (ii) intramolecular cyclodehydrogenation of the resultingo-hydroxychalcones. The reaction conditions are discussed herein.
- Chang, Meng-Yang,Tsai, Min-Chen,Lin, Chun-Yi
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p. 11655 - 11662
(2021/03/31)
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- Correlation study on methoxylation pattern of flavonoids and their heme-targeted antiplasmodial activity
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A library of 33 polymethoxylated flavones (PMF) was evaluated for heme-binding affinity by biomimetic MS assay and in vitro antiplasmodial activity on two strains of P. falciparum. Stability of heme adducts was discussed using the dissociation voltage at 50% (DV50). No correlation was observed between the methoxylation pattern and the antiparasitic activity, either for the 3D7 chloroquine-sensitive or for the W2 chloroquine-resistant P. falciparum strains. However, in each PMF family an increased DV50 was observed for the derivatives methoxylated in position 5. Measurement of intra-erythrocytic hemozoin formation of selected derivatives was performed and hemozoin concentration was inversely correlated with heme-binding affinity. Kaempferol showed no influence on hemozoin formation, reinforcing the hypothesis that this compound may exert in vitro antiplasmodial activity mostly through other pathways. Pentamethoxyquercetin has simultaneously demonstrated a significant biological activity and a strong interaction with heme, suggesting that inhibition of hemozoin formation is totally or partially responsible for its antiparasitic effect.
- Boutefnouchet, Sabrina,Bouzidi, Chouaha,Cojean, Sandrine,Figadère, Bruno,Grougnet, Rapha?l,Maciuk, Alexandre,Michel, Sylvie,Ortiz, Sergio,Vásquez-Ocmín, Pedro G.
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- PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING DIABETES COMPLICATIONS COMPRISING NOVEL CHRYSIN DERIVATIVE COMPOUND AS ACTIVE INGREDIENT
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Disclosed is a pharmaceutical composition for preventing or treating diabetes complications containing a novel chrysin derivative compound as an active ingredient, and more specifically, a pharmaceutical composition for preventing or treating diabetes complications containing, as an active ingredient, a novel chrysin derivative compound that is capable of preventing or treating diabetes complications due to the ability thereof to inhibit the formation of an advanced glycation end-product (AGE).
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Paragraph 0042; 0047-0049
(2020/12/16)
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- New alkoxy flavone derivatives targeting caspases: Synthesis and antitumor activity evaluation
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The antitumor activity of natural flavonoids has been exhaustively reported. Previously it has been demonstrated that prenylation of flavonoids allows the discovery of new compounds with improved antitumor activity through the activation of caspase-7 activity. The synthesis of twenty-five flavonoids (4-28) with one or more alkyl side chains was carried out. The synthetic approach was based on the reaction with alkyl halide in alkaline medium by microwave (MW) irradiation. The in vitro cell growth inhibitory activity of synthesized compounds was investigated in three human tumor cell lines. Among the tested compounds, derivatives 6, 7, 9, 11, 13, 15, 17, and 18 revealed potent growth inhibitory activity (GI50 10 μM), being the growth inhibitory effect of compound 13 related with a pronounced caspase-7 activation on MCF-7 breast cancer cells and yeasts expressing human caspase-7. A quantitative structure-activity relationship (QSAR) model predicted that hydrophilicity, pattern of ring substitution/shape, and presence of partial negative charged atoms were the descriptors implied in the growth inhibitory effect of synthesized compounds. Docking studies on procaspase-7 allowed predicting the binding of compound 13 to the allosteric site of procaspase-7.
- Moreira, Joana,Ribeiro, Diana,Silva, Patrícia M. A.,Nazareth, Nair,Monteiro, Madalena,Palmeira, Andreia,Saraiva, Lucília,Pinto, Madalena,Bousbaa, Hassan,Cidade, Honorina
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- Scope and Mechanism of the Ruthenium-Catalyzed Dehydrative C-H Coupling of Phenols with α,β-Unsaturated Carbonyl Compounds: Expedient Synthesis of Chromene and Benzoxacyclic Derivatives
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Chromene and benzoxacyclic derivatives were efficiently synthesized from the ruthenium-catalyzed dehydrative C-H coupling reaction of phenols with α,β-unsaturated carbonyl compounds. The cationic ruthenium-hydride complex was found to be an effective catalyst for the coupling and annulation of phenols with enals to form chromene products. The coupling of phenols with linear enones afforded 2,4-disubstituted chromene derivatives, whereas the analogous coupling with cyclic enones yielded 9-hydroxybenzoxazole products. The reaction of 3,5-dimethoxyphenol with PhCH=CHCDO resulted in the chromene product with a significant H/D exchange to both benzylic and vinyl positions. The most significant carbon isotope effect from the coupling of 3,5-dimethoxyphenol with 4-methoxycinnamaldehyde was observed on the α-olefinic carbon of the chromene product (C(2) = 1.067). A Hammett plot from the coupling of 3,5-dimethoxyphenol with para-substituted p-X-C6H4CH=CHCHO displayed a linear correlation, with a strong promotional effect by an electron-withdrawing group (ρ = +1.5; X = OCH3, CH3, H, F, Cl). Several biologically active chromenone derivatives were synthesized by using the catalytic coupling method. The catalytic method provides an expedient synthetic protocol for the coupling of phenols with α,β-unsaturated carbonyl compounds without employing reactive reagents or forming any wasteful byproducts.
- Mokar, Bhanudas Dattatray,Yi, Chae S.
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p. 4625 - 4632
(2019/12/24)
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- Structure–activity relationships of flavanones, flavanone glycosides, and flavones in anti-degranulation activity in rat basophilic leukemia RBL-2H3 cells
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The incidence of type I allergies, which are associated with mast cell degranulation and local inflammation, is increasing, and new treatments are needed. To date, structure–activity relationships of flavonoids in their degranulation-inhibiting activity have not been systematically characterized. In the current study, the degranulation-inhibiting activity of a series of flavonoids was evaluated. The following three observations were made: (1) the activity disappears when a sugar moiety is introduced into the A ring of the flavanone; (2) the activity depends on the number of hydroxyl groups on the B ring; (3) the activity is markedly enhanced when a double bond is introduced into the C ring. The information obtained in the current study may guide the development of a therapy for type I allergies.
- Noshita, Toshiro,Miura, Kaori,Ikeda, Kaoru,Ouchi, Hidekazu,Matsumoto, Takuya,Tai, Akihiro
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p. 551 - 556
(2018/01/27)
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- Synthesis of Benzopyran-Fused Flavone Derivatives via Microwave-Assisted Intramolecular C-H Activation
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A microwave-assisted intramolecular direct arylation method for the synthesis of benzopyran-fused flavone derivatives containing natural flavone backbones is described. Different polyalkoxy flavones were synthesized and functionalized with 2-bromobenzyl bromide. The resulting compounds were subjected to palladium-catalyzed intramolecular direct arylation reactions supported by microwave irradiation to produce fused tetracyclic flavones. In the case of the 7-substituted chrysin derivative, the regioselectivity of the coupling was also examined.
- Sipos, Zoltán,Kónya, Krisztina
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p. 1610 - 1620
(2018/03/21)
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- Anti-glycation, carbonyl trapping and anti-inflammatory activities of chrysin derivatives
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The aim of this study was searching anti-glycation, carbonyl trapping and anti-inflammatory activities of chrysin derivatives. The inhibitory effect of chrysin on advanced glycation end-products (AGEs) was investigated by trapping methylglyoxal (MGO), and MGO-conjugated adducts of chrysin were analyzed using LC-MS/MS. The mono- or di-MGO-conjugated adducts of chrysin were present at 63.86 and 29.69% upon 48 h of incubation at a chrysin:MGO ratio of 1:10. The MGO adducted positions on chrysin were at carbon 6 or 6 & 8 in the A ring by classic aldol condensation. To provide applicable knowledge for developing chrysin derivatives as AGE inhibitors, we synthesized several O-alkyl or ester derivatives of chrysin and compared their AGE formation inhibitory, anti-inflammatory, and water solubility characteristics. The results showed that 5,7-di-O-acetylchrysin possessed higher AGE inhibitory and water solubility qualities than original chrysin, and retained the anti-inflammation activity. These results suggested that 5,7-di-O-acetylchrysin could be a potent functional food ingredient as an AGE inhibitor and anti-inflammatory agent, and promotes the development of the use of chrysin in functional foods.
- Hwang, Seung Hwan,Kim, Hyun Yong,Zuo, Guanglei,Wang, Zhiqiang,Lee, Jae-Yong,Lim, Soon Sung
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- 2-substituted benzopyran-4-one compounds and application thereof
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The invention relates to the technical field of medicine and discloses 2-substituted benzopyran-4-one compounds with a structure shown in general formula I and an application of the compounds in preparation of antifungal drugs and synergistic antifungal drugs. The compounds can be jointly used with azole antifungal drugs, can improve sensibility of drug-resistance bacteria to the azole drugs, reverses drug resistance and produces a synergistic antifungal function.
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Paragraph 0146; 0147; 0148; 0175; 0176; 0177
(2016/10/08)
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- Synthesis and biological evaluation of novel 7-O-lipophilic substituted baicalein derivatives as potential anticancer agents
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We synthesized derivatives of baicalein, wogonin, and chrysin through alkylation at the 7-O-position of the A ring with lipophilic terphenyl or long chain n-alkyl groups, and studied the in vitro anticancer activity of the derivatives through the growth inhibition MTT assay. We discovered that baicalein and two of its derivatives were good free radical scavengers. Among the 20 synthesized derivatives, 7-O-farnesylbaicalein (5d) and 7-O-dodecylbaicalein (5i) demonstrated stronger growth inhibition against human colon cancer SW480 cells compared with baicalein, with half maximal inhibitory concentration (IC50) values of 1.15 and 1.57 μM, respectively. Furthermore, 5d and 5i dose- and time-dependently inhibited the growth of SW480 cells. Cell cycle distribution analysis showed that 5d and 5i induced SW480 cell arrest at the S phase through an apoptotic mechanism, which was associated with an increase in the generation of reactive oxygen species. In conclusion, the potent anticancer activity of the baicalein derivatives (5d and 5i) suggested that the derivatives are potential anticancer agents for human colon cancer.
- Wang, Shao-Hung,Chen, Ching-Hsein,Lo, Chih-Yu,Feng, Ji-Zhen,Lin, Hong-Jhih,Chang, Po-Ya,Yang, Ling-Ling,Chen, Lih-Geeng,Liu, Yi-Wen,Kuo, Cheng-Deng,Wu, Jin-Yi
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supporting information
p. 1864 - 1873
(2015/10/20)
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- Facile formation of methylenebis(chalcone)s through unprecedented methylenation reaction. Application to antiparasitic and natural product synthesis
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The formation of methylenebis(chalcone)s has been discovered during deprotection with methoxymethyl groups from trihydroxychalcones. Studies on this methylenation reaction led to a mechanism hypothesis that was extended to other chalcones and to dihydrochalcone, acetophenone, benzophenone and flavone derivatives. This new method was applied to the rapid synthesis of natural product piperanduncin C. These original methylenebis compounds were also evaluated for their antiparasitic activity. Copyright
- Thevenin, Marion,Mouray, Elisabeth,Grellier, Philippe,Dubois, Joelle
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supporting information
p. 2986 - 2992
(2014/05/20)
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- Synthesis and evaluation of selenoflavones that have potential neuroprotective effects
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We synthesized selenoflavones and evaluated their physicochemical properties and antioxidant effects. When oxygen was substituted with selenium, the compounds exhibited improved polarity and lipophilicity, implying that this change could lead to better BBB penetration. Selenoflavones revealed more potent antioxidant activity in our in-vitro assay. This suggests that selenoflavones would be more druggable than flavones and have a better potential as a neuroprotective agent.
- Choi, Yong-Sung,Kim, Yoon-Jung,Lee, Ju Yeun,Lee, Jinu,Jeong, Jin-Hyun
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p. 2794 - 2805
(2015/03/04)
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- Regioselective iodination of flavonoids by N-iodosuccinimide under neutral conditions
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Regioselective synthesis of C-6 and C-8 monoiodo flavonoids, which are important intermediates for the synthesis of flavonoid natural products and drug molecules, was achieved by iodination of suitably alkylated flavonoids with N-iodosuccinimide (NIS) in DMF. The iodination gives either a C-6 or C-8 iodo flavonoid in high yield, depending on the protection pattern of the C-5 and C-7 OH groups. The mild and neutral conditions render this novel protocol particularly useful for the regioselective iodination of acid-sensitive substrates.
- Lu, Kui,Chu, Jie,Wang, Haomeng,Fu, Xiaoli,Quan, Dewu,Ding, Hongxia,Yao, Qingwei,Yu, Peng
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supporting information
p. 6345 - 6348
(2013/11/06)
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- A convenient and safe O-methylation of flavonoids with dimethyl carbonate (DMC)
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Dietary flavonoids exhibit beneficial health effects. Several epidemiological studies have focused on their biological activities, including antioxidant, antibacterial, antiviral, anti-inflammatory and cardiovascular properties. More recently, these compounds have shown to be promising cancer chemopreventive agents in cell culture studies. In particular, O-methylated flavonoids exhibited a superior anticancer activity than the corresponding hydroxylated derivatives being more resistant to the hepatic metabolism and showing a higher intestinal absorption. In this communication we describe a convenient and efficient procedure in order to prepare a large panel of mono- and dimethylated flavonoids by using dimethyl carbonate (DMC), an ecofriendly and non toxic chemical, which plays the role of both solvent and reagent. In order to promote the methylation reaction under mild and practical conditions, 1,8-diazabicyclo[5.4.0]undec-7- ene (DBU) was added in the solution; methylated flavonoids were isolated in high yields and with a high degree of purity. This methylation protocol avoids the use of hazardous and high toxic reagents (diazomethane, dimethyl sulfate, methyl iodide).
- Bernini, Roberta,Crisante, Fernanda,Ginnasi, Maria Cristina
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experimental part
p. 1418 - 1425
(2011/04/25)
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- Use of acyl substituents to favour 2,3-epoxidation of 5,7-dioxygenated flavones with dimethyldioxirane
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The reaction of 5,7-dimethoxyflavone with dimethyldioxirane (DMDO) gives the 2,3-epoxide rapidly at first. However, low levels of ring A hydroxylated by-products are also formed. With increasing proportions of DMDO, demethylation at C-5 becomes apparent and consumption of substrate is not matched by further significant build-up of the epoxide. Deactivation of ring A by the use of acyl groups removes this complication. 5,7-Diacylflavones give excellent yields of epoxides and monoacyl derivatives also react in good yield. Ionization potential maps derived from density functional theory calculations (B3LYP/6-31G), provide good visual indicators of the relative reactivity of the key nucleophilic loci. The epoxides may be isolated as such, or transformed into flavonols by treatment with p-toluenesulfonic acid.
- Compton, Benjamin J.,Larsen, Lesley,Weavers, Rex T.
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scheme or table
p. 718 - 726
(2011/03/19)
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- Convergent synthesis of mosloflavone, negletein and baicalein from crysin
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An expeditious synthesis of three polyoxygenated flavones: mosloflavone, negletein and baicalein, starting from crysin, an easily available flavone, by a bromination/methoxylation procedure is reported. The convergent synthesis exploits a base induced Wesley-Moser type rearrangement.
- Righi, Giuliana,Antonioletti, Roberto,Silvestri, Ilaria Proietti,D'Antona, Nicola,Lambusta, Daniela,Bovicelli, Paolo
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experimental part
p. 1294 - 1298
(2010/04/02)
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- C-isoprenylation of flavonoids enhances binding affinity toward P-glycoprotein and modulation of cancer cell chemoresistance
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Previous studies have shown that flavones bind to P-glycoprotein (Pgp) with higher affinity than isoflavones, flavanones, and glycosylated derivatives. In the present work, a series of C- or O-substituted hydrophobic derivatives of chrysin were synthesized to further investigate structural requirements of the A ring toward Pgp modulation. Increasing hydrophobicity at either position 6, 8, or 7 increased the affinity of in vitro binding to a purified cytosolic domain of Pgp, but only benzyl and 3,3-dimethylallyl C-substitution produced a high maximal quenching of the protein intrinsic fluorescence. Inhibition of membrane Pgp within leukemic cells, characterized by intracellular drug accumulation, was specifically produced by isoprenylated derivatives, with 8-(3,3-dimethylallyl)chrysin being even more efficient than the commonly used cyclosporin A.
- Comte,Daskiewicz,Bayet,Conseil,Viornery-Vanier,Dumontet,Di Pietro,Barron
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p. 763 - 768
(2007/10/03)
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- Synthesis and hypoglycemic effect of chrysin derivatives
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A series of 18 chrysin derivatives, prepared by alkylation and condensation, were fully characterized by NMR and other techniques and tested in vivo against the diabetes mellitus. Several modified compounds especially those with propyl, butyl, octyl and tolyl groups were found to have hypoglycemic effect on diabetic mice in spite of the fact that chrysin itself had inhibited insulin release by 40-60%. None of the test animals died at the maximum dose 500mg/kg and did not cause any significant change in general feature, water and food consumption, body weight and organ weight when we examined the acute oral toxicity of those compounds having significant hypoglycemic effect.
- Shin, Joon-Su,Kim, Kyoung-Soon,Kim, Myoung-Bohm,Jeong, Jae-Hoon,Kim, Bak-Kwang
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p. 869 - 874
(2007/10/03)
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- Reactions of 4,6-Bis(acetyl)resorcinol with Alkoxycarbonylalkylidene(triphenyl)phosphoranes. Preparation of Coumarin Derivatives
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Reaction of compound 1 with ylide 2a affords compounds 3a,3b and coumarins 4a,5a, 5b, 6a in 77percent total yield.Reaction of 1 with ylide 2b affords coumarin 4b.The acetylderivatives obtained, react further with ylides 2a-c to give pyranochromene-2,8-diones 6b-d.
- Nicolaides, D. N.,Fylaktakidou, K. C.,Bezergiannidou-Balouktsi, C.,Litinas, K. E.
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p. 173 - 176
(2007/10/02)
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- FLAVONOID 5-GLUCOSIDES FROM PRUNUS CERASUS BARK AND THEIR CHARACTERISTIC WEAK GLYCOSIDIC BONDING
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Pinostrobin 5-glucoside, a novel flavanone glycoside, was isolated from the bark of Prunus cerasus.As it was not found in P. avium, the substance is useful to distinguish these two species.Apigenin 5-glucoside, genkwanin 5-glucoside and neosakuranin were also isolated from the bark of P. cerasus.They occur in both species as minor components.These 5-glucosides together with genistein 5-glucoside, prunetin 5-glucoside, sakuranin, tectochrysin 5-glucoside and luteolin 5-glucoside were hydrolysed in malic acid.The isoflavone and flavone 5-glucosides were shown to be hydrolysed more rapidly than the flavanone 5-glucosides, whereas no hydrolysis was observed with the corresponding 7-glucosides under the same conditions.The chalcone 2'-glucoside neosakuranin was transformed at first to the corresponding flavanone 5-glucoside, which was hydrolysed thereafter. Key Word Index - Prunus cerasus; Prunus avium; Rosaceae; bark; pinostrobin 5-glucoside; flavonoid 5-glucosides; hydrolysis.
- Geibel, Martin,Feucht, Walter
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p. 1519 - 1521
(2007/10/02)
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- Pyrolitic Elimination of Hydrogen Halide and Halogen from 2,3-Dihalogenoketones
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The thermal elimination of hydrogen chloride from 2'-hydroxychalcone dichlorides occured in two stages, initially forming 3-chloroflavones and then flavones; α-chloro-2'-hydroxychalcones, the likely intermediates in the formation of 3-chloroflavones, also yielded the same products.The pyrolysis of 2'-hydroxychalcone dibromides resulted in debromination as well as dehydrobromination with the consequent appearence of brominated flavones among the products.The formation of 3-bromoflavones was not observed but the isomeric (E)-α-bromo-2'-hydroxychalcones thermally isomerized to their (Z)-isomers and then underwent cyclization and dehydrobromination.The bromide were considerably more reactive than the dichlorides but, as a synthetic procedure, the pyrolysis of the dichlorides is cleaner and more productive.
- Donnely, John A.,Quigley, Killian
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p. 1299 - 1305
(2007/10/02)
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