5631-70-9Relevant academic research and scientific papers
Size and branching effects on the fluorescence of benzylic dendrimers possessing one apigenin fluorophore at the core
Vin?, Petr,Vermachová, Martina,Dra?ar, Pavel,Del Barrio, Melisa,Jarne, Carmen,Cebolla, Vicente L.,De Cózar, Abel,Zangi, Ronen,Cossío, Fernando P.
, p. 10361 - 10368 (2013)
Different generations of dendrimers incorporating one fluorescent core of apigenin and three Fréchet benzylic dendrons have been prepared. The chief geometric features of these dendrimers have been obtained by Molecular Dynamics simulations. These computa
Discovery of Novel Apigenin-Piperazine Hybrids as Potent and Selective Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors for the Treatment of Cancer
Long, Huan,Hu, Xiaolong,Wang, Baolin,Wang, Quan,Wang, Rong,Liu, Shumeng,Xiong, Fei,Jiang, Zhenzhou,Zhang, Xiao-Qi,Ye, Wen-Cai,Wang, Hao
, p. 12089 - 12108 (2021/09/06)
Poly (ADP-ribose) polymerase-1 (PARP-1) is a potential target for the discovery of chemosensitizers and anticancer drugs. Amentoflavone (AMF) is reported to be a selective PARP-1 inhibitor. Here, structural modifications and trimming of AMF have led to a series of AMF derivatives (9a-h) and apigenin-piperazine/piperidine hybrids (14a-p, 15a-p, 17a-h, and 19a-f), respectively. Among these compounds, 15l exhibited a potent PARP-1 inhibitory effect (IC50 = 14.7 nM) and possessed high selectivity to PARP-1 over PARP-2 (61.2-fold). Molecular dynamics simulation and the cellular thermal shift assay revealed that 15l directly bound to the PARP-1 structure. In in vitro and in vivo studies, 15l showed a potent chemotherapy sensitizing effect against A549 cells and a selective cytotoxic effect toward SK-OV-3 cells through PARP-1 inhibition. 15l·2HCl also displayed good ADME characteristics, pharmacokinetic parameters, and a desirable safety margin. These findings demonstrated that 15l·2HCl may serve as a lead compound for chemosensitizers and the (BRCA-1)-deficient cancer therapy.
Divergent synthesis of flavones and flavanones from 2′-hydroxydihydrochalconesviapalladium(ii)-catalyzed oxidative cyclization
Son, Seung Hwan,Cho, Yang Yil,Yoo, Hyung-Seok,Lee, Soo Jin,Kim, Young Min,Jang, Hyu Jeong,Kim, Dong Hwan,Shin, Jeong-Won,Kim, Nam-Jung
, p. 14000 - 14006 (2021/04/22)
Divergent and versatile synthetic routes to flavones and flavanonesviaefficient Pd(ii) catalysis are disclosed. These Pd(ii) catalyses expediently provide a variety of flavones and flavanones from 2′-hydroxydihydrochalcones as common intermediates, depending on oxidants and additives,viadiscriminate oxidative cyclization sequences involving dehydrogenation, respectively, in a highly atom-economic manner.
Flavonoid-based inhibitors of the Phi-class glutathione transferase from black-grass to combat multiple herbicide resistance
Brazier-Hicks, Melissa,Coxon, Christopher R.,Cummins, Ian,Edwards, Robert,Eno, Rebecca F. M.,Freitag-Pohl, Stefanie,Hughes, David J.,Mitchell, Glynn,Moore, Jenny,Onkokesung, Nawaporn,Pohl, Ehmke,Schwarz, Maria,Steel, Patrick G.,Straker, Hannah E.,Wortley, David J.
, p. 9211 - 9222 (2021/11/16)
The evolution and growth of multiple-herbicide resistance (MHR) in grass weeds continues to threaten global cereal production. While various processes can contribute to resistance, earlier work has identified the phi class glutathione-S-transferase (AmGSTF1) as a functional biomarker of MHR in black-grass (Alopecurus myosuroides). This study provides further insights into the role of AmGSTF1 in MHR using a combination of chemical and structural biology. Crystal structures of wild-type AmGSTF1, together with two specifically designed variants that allowed the co-crystal structure determination with glutathione and a glutathione adduct of the AmGSTF1 inhibitor 4-chloro-7-nitro-benzofurazan (NBD-Cl) were obtained. These studies demonstrated that the inhibitory activity of NBD-Cl was associated with the occlusion of the active site and the impediment of substrate binding. A search for other selective inhibitors of AmGSTF1, using ligand-fishing experiments, identified a number of flavonoids as potential ligands. Subsequent experiments using black-grass extracts discovered a specific flavonoid as a natural ligand of the recombinant enzyme. A series of related synthetic flavonoids was prepared and their binding to AmGSTF1 was investigated showing a high affinity for derivatives bearing a O-5-decyl-α-carboxylate. Molecular modelling based on high-resolution crystal structures allowed a binding pose to be defined which explained flavonoid binding specificity. Crucially, high binding affinity was linked to a reversal of the herbicide resistance phenotype in MHR black-grass. Collectively, these results present a nature-inspired new lead for the development of herbicide synergists to counteract MHR in weeds. This journal is
Synthesis method of isolicoflavonol
-
Paragraph 0111; 0239-0245, (2020/12/29)
The invention provides a synthesis method of isolicoflavonol, which comprises the following steps: carrying out condensation reaction on 2,4-O-R1(protective group, the same below)-6-hydroxyacetophenone and 4-O-R2(protective group, the same below)-benzaldehyde to generate 2',4'-O-R1-6'-hydroxy-4-O-R2-chalcone; oxidizing the chalcone to generate flavonol; carrying out selective protection on 3-OH ofthe flavonol to obtain 3,5,7-O-R1-4'-O-R2-flavonol; removing the protecting group R2 from the 3,5,7-O-R1-4'-O-R2-flavonol to obtain 3,5,7-O-R1-4'-hydroxyflavonol; carrying out 1,1-dimethylpropargyl reaction on the 4,4'-OH site to obtain 3,5,7-O-R1-4'-O-(1',1''-dimethyl propargyl)flavonol; carrying out partial hydrogenation on the alkynyl of the 3,5,7-O-R1-4'-O-(1',1''-dimethyl propargyl)flavonolunder the action of a catalyst to obtain 3,5,7-O-R1-4'-O-(1',1''-dimethylpropenyl)flavonol and carrying out Claisen rearrangement on the 3,5,7-O-R1-4'-O-(1',1''-dimethylpropenyl)flavonol to obtain 3,5,7-O-R1-isolicoflavonol, and removing the protecting group R1 from the 3,5,7-O-R1-isolicoflavonol to obtain the isolicoflavonol.
Correlation study on methoxylation pattern of flavonoids and their heme-targeted antiplasmodial activity
Boutefnouchet, Sabrina,Bouzidi, Chouaha,Cojean, Sandrine,Figadère, Bruno,Grougnet, Rapha?l,Maciuk, Alexandre,Michel, Sylvie,Ortiz, Sergio,Vásquez-Ocmín, Pedro G.
, (2020/09/16)
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.
Novel chromenone derivatives having substituted biphenyl group and a pharmaceutical composition for prevention or treatment of allergic diseases compring the same
-
Paragraph 0103-0110; 0112-0116, (2020/11/26)
The present invention relates to: a novel chromenone derivative compound capable of effectively suppressing an allergic immune response by inhibiting signal transduction mediated by thymic stromal lymphopoietin (TSLP); and a pharmaceutical composition capable of fundamentally preventing or treating various allergic diseases by using the same.COPYRIGHT KIPO 2021
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
Mokar, Bhanudas Dattatray,Yi, Chae S.
, p. 4625 - 4632 (2019/12/24)
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.
Synthesis of Benzopyran-Fused Flavone Derivatives via Microwave-Assisted Intramolecular C-H Activation
Sipos, Zoltán,Kónya, Krisztina
, p. 1610 - 1620 (2018/03/21)
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.
First Total Synthesis of Original Chalcone–Flavone Dimers as Cissampeloflavone Analogues
Thévenin, Marion,Thoret, Sylviane,Dubois, Jo?lle
, p. 5843 - 5852 (2018/11/24)
The total synthesis of furoflavones closely related to the natural product cissampeloflavone was explored following different pathways. The involvement of a flavone as a key intermediate proved to be the most efficient way to form the 7-phenyl-5H-furo[3,2-g]chromen-5-one scaffold, and the first example of furoflavone formation was achieved in this way. For the synthesis of chalcone–flavone dimers, two different strategies were examined: either acylation at the very end of the synthesis, or introduction of the 3-acyl group during furan-ring formation. The final acylation was hardly achievable with hindered benzoyl chlorides, but a simpler 4-methoxybenzoyl group was added to the furoflavone in modest yield. The alternative direct introduction of this acyl group during furan formation proved to be more efficient. Conjugate addition of an iodoflavone to an ynone followed by intramolecular Heck cyclization gave the best results, leading to the first synthetic chalcone–flavone dimer ever described.
