65548-54-1Relevant articles and documents
Diversity-oriented synthesis of pyrazoles derivatives from flavones and isoflavones leads to the discovery of promising reversal agents of fluconazole resistance in Candida albicans
Cui, Chang-Yi,Liu, Jun,Zheng, Hong-Bo,Jin, Xue-Yang,Zhao, Xiao-Yu,Chang, Wen-Qiang,Sun, Bin,Lou, Hong-Xiang
supporting information, p. 1545 - 1549 (2018/04/02)
Diversity-oriented synthesis of derivatives of natural products is an important approach for the discovery of novel drugs. In this paper, a series of novel 3,4-diaryl-1H-pyrazoles and 3,5-diaryl-1H-pyrazoles derivatives were synthesized through the one-po
Novel synthesised flavone derivatives provide significant insight into the structural features required for enhanced anti-proliferative activity
Ravishankar, Divyashree,Watson, Kimberly A.,Greco, Francesca,Osborn, Helen M. I.
, p. 64544 - 64556 (2016/07/21)
With many cancers showing resistance to current chemotherapies, the search for novel anti-cancer agents is attracting considerable attention. Natural flavonoids have been identified as useful leads in such programmes. However, since an in-depth understanding of the structural requirements for optimum activity is generally lacking, further research is required before the full potential of flavonoids as anti-proliferative agents can be realised. Herein a broad library of 76 methoxy and hydroxy flavones, and their 4-thio analogues, was constructed and their structure-activity relationships for anti-proliferative activity against the breast cancer cell lines MCF-7 (ER +ve), MCF-7/DX (ER +ve, anthracycline resistant) and MDA-MB-231 (ER -ve) were probed. Within this library, 42 compounds were novel, and all compounds were afforded in good yields and >95% purity. The most promising lead compounds, specifically the novel hydroxy 4-thioflavones 15f and 16f, were further evaluated for their anti-proliferative activities against a broader range of cancer cell lines by the National Cancer Institute (NCI), USA and displayed significant growth inhibition profiles (e.g. compound-15f: MCF-7 (GI50 = 0.18 μM), T-47D (GI50 = 0.03 μM) and MDA-MB-468 (GI50 = 0.47 μM) and compound-16f: MCF-7 (GI50 = 1.46 μM), T-47D (GI50 = 1.27 μM) and MDA-MB-231 (GI50 = 1.81 μM)). Overall, 15f and 16f exhibited 7-46 fold greater anti-proliferative potency than the natural flavone chrysin (2d). A systematic structure-activity relationship study against the breast cancer cell lines highlighted that free hydroxyl groups and the B-ring phenyl groups were essential for enhanced anti-proliferative activities. Substitution of the 4-CO functionality with a 4-CS functionality, and incorporation of electron withdrawing groups at C-4′ of the B-ring phenyl, also enhanced activity. Molecular docking and mechanistic studies suggest that the anti-proliferative effects of flavones 15f and 16f are mediated via ER-independent cleavage of PARP and downregulation of GSK-3β for MCF-7 and MCF-7/DX cell lines. For the MDA-MB-231 cell line, restoration of the wild-type p53 DNA binding activity of mutant p53 tumour suppressor gene was indicated.
Towards tropomyosin-related kinase B (TrkB) receptor ligands for brain imaging with PET: Radiosynthesis and evaluation of 2-(4-[18F] fluorophenyl)-7,8-dihydroxy-4H-chromen-4-one and 2-(4-([N-methyl- 11C]-dimethylamino)phenyl)-7,8-dihydroxy-4H-chromen-4-one
Bernard-Gauthier, Vadim,Boudjemeline, Mehdi,Rosa-Neto, Pedro,Thiel, Alexander,Schirrmacher, Ralf
, p. 7816 - 7829 (2014/01/06)
The interaction of tropomyosin-related kinase B (TrkB) with the cognate ligand brain-derived neurotrophic factor (BDNF) mediates fundamental pathways in the development of the nervous system. TrkB signaling alterations are linked to numerous neurodegenerative diseases and conditions. Herein we report the synthesis, biological evaluation and radiosynthesis of the first TrkB radioligands based on the recently identified 7,8-dihydroxyflavone chemotype. 2-(4-[18F]fluorophenyl)-7,8-dihydroxy-4H-chromen-4-one ([ 18F]10b) was synthesized in high radiochemical yields via an efficient SNAr radiofluorination involving a para-Michael acceptor substituted aryl followed by BBr3-promoted double demethylation. Selective N-[11C]methylation afforded 2-(4-([N-methyl- 11C]-dimethylamino)phenyl)-7,8-dihydroxy-4H-chromen-4-one ([ 11C]10c) from the fully deprotected catechol-bearing normethyl precursor 13 with [11C]MeOTf. In vitro autoradiography of [ 18F]10b with transverse rat brain sections revealed high specific binding in the cortex, striatum, hippocampus and thalamus in accordance with expected TrkB distribution. Blockade experiments with both 7,8-dihydroxyflavone (1a) and TrkB cognate ligand, BDNF, led to decreases of 80% and 85% of radioligand binding strongly supporting the hypothesis that 7,8- dihydroxyflavones exert their effect on TrkB phosphorylation via direct TrkB extracellular domain (ECD) binding. Positron emission tomography (PET) studies revealed that [18F]10b and [11C]10c brain uptake is minimal and that they are rapidly eliminated from the plasma (effective plasma half-life 5-10 min) via hepatic secretion. Nevertheless, the high specific binding and TrkB specificity derived from in vitro experiments suggests that the 7,8-disubstituted flavone chemotype represents a promising scaffold for the development of TrkB radiotracers for PET.
Characterization of two candidate flavone 8-O-methyltransferases suggests the existence of two potential routes to nevadensin in sweet basil
Berim, Anna,Gang, David R.
, p. 33 - 41 (2013/10/21)
Regioselective 6-,7-,8-,3'-, and 4'-O-methylations underlie the structural diversity of lipophilic flavones produced in the trichomes of sweet basil (Ocimum basilicum L.). The positions 6, 7, and 4' are methylated by a recently described set of cation-independent enzymes. The roles of cation-dependent O-methyltransferases still require elucidation. Here, the basil trichome EST database was used to identify a Mg2+-dependent O-methyltransferase that was likely to accept flavonoids as substrates. The recombinant protein was found to be active with a wide range of o-diphenols, and methylated the 8-OH moiety of the flavone backbone with higher catalytic efficiency than the 3'-OH group of candidate substrates. To further investigate flavone 8-O-methylation, the activity of a putative cation-independent flavonoid 8-O-methyltransferase from the same EST collection was assessed with available substrate analogs. Notably, it was strongly inhibited by gardenin B, one of its expected products. The catalytic capacities of the two studied proteins suggest that two alternative routes to nevadensin, a major flavone in some basil cultivars, might exist. Correlating the expression of the underlying genes with the accumulation of 8-substituted flavones in four basil lines did not clarify which is the major operating pathway in vivo, yet the combined data suggested that the biochemical properties of flavone 7-O-demethylase could play a key role in determining the reaction order.
Selective and efficient oxidative modifications of flavonoids with 2-iodoxybenzoic acid (IBX)
Barontini, Maurizio,Bernini, Roberta,Crisante, Fernanda,Fabrizi, Giancarlo
experimental part, p. 6047 - 6053 (2010/09/11)
2-Iodoxybenzoic acid (IBX), a mild and efficient hypervalent iodine oxidant, has been utilised in different reaction conditions to perform several efficient oxidative modifications of flavonoids. Fine-tuning of the reaction conditions allowed remarkably selective modifications of these compounds. At room temperature, IBX proved to be an excellent reagent for a highly regioselective aromatic hydroxylation of monohydroxylated flavanones and flavones, generating the corresponding catecholic derivatives showing high antioxidant activity. At 90 °C, IBX efficiently dehydrogenated a large panel of methoxylated flavanones to their corresponding flavones exhibiting anticancer activity. IBX polystyrene has also been utilised to increase the recovery of highly polar compounds. Following the first oxidation, the reagent was recovered and reused in several runs without loss of efficiency and selectivity. The first example of an application of IBX polystyrene in a dehydrogenation reaction has been described.
Substituted benzopyranones as telomerase inhibitors
-
, (2008/06/13)
The present invention relates to benzopyranone derivatives, to methods for treating telomerase-modulated diseases, in particular cancers, with said derivatives, to a process for their preparation, to their use as medicaments and to pharmaceutical compositions comprising them.
An efficient conversion of 2'-hydroxychalcones into flavanones: Use of tetra-n-butylammonium iodide
Dhawan, Deepika,Grover, S. K.
, p. 73 - 74 (2007/10/03)
2'-Hydroxychalcones 1 possessing different substitution patterns in rings A and B, have been found to undergo efficient isomerization to the corresponding flavanones 2 when heated in ethanol with hydrochloric acid and tetra-n-butylammonium iodide.
An efficient conversion of 2'-hydroxychalcones to flavones
Hans,Grover
, p. 1021 - 1023 (2007/10/02)
2'-Hydroxychalcones have been found to undergo smooth conversion to flavones when heated with sodium periodate in dimethyl sulphoxide.
