38183-03-8Relevant articles and documents
Preparation method of 7,8-dihydroxy flavone
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, (2020/07/13)
The invention relates to a preparation method of 7,8-dihydroxy flavone, and belongs to the technical field of synthesis of medical intermediates. The preparation method comprises the following steps:by taking pyrogallol as a raw material, introducing an acetyl group to synthesize DHF1; protecting three phenolic hydroxyl groups to synthesize DHF2; selectively reducing the ortho-hydroxyl group of the acetyl group to synthesize DHF3; carrying out an aldol condensation reaction on DHF3 and benzaldehyde to prepare DHF4; carrying out a cyclization reaction under the condition of iodine catalysis toobtain DHF5; and finally carrying out a hydrolysis reaction to generate the final product. The method is simple and convenient to operate, reasonable in reaction process, low in production cost, goodin product quality, free of environmental pollution and suitable for industrial production, wherein the content of the product is higher than 98%.
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.
Synthesis of Diverse Oxa-Carbocycle-Annulated Flavones Using the Combined Claisen Rearrangement and Ring-Closing Metathesis
Gogula, Thirupathi,Yerrabelly, Jayaprakash Rao
, p. 547 - 557 (2016/07/22)
A simple and efficient route for the synthesis of oxepine-, oxocine-, oxepinone-, and dioxocine-angularly annulated flavone skeletons has been developed. The combined Claisen rearrangement and the ring-closing metathesis are used as key steps for the construction of C7/C8–C6–C6tricyclic core structures.
Antimalarial activity of HIV-1 protease inhibitor in chromone series
Lerdsirisuk, Pradith,Maicheen, Chirattikan,Ungwitayatorn, Jiraporn
, p. 142 - 147 (2015/02/05)
Increasing parasite resistance to nearly all available antimalarial drugs becomes a serious problem to human health and necessitates the need to continue the search for new effective drugs. Recent studies have shown that clinically utilized HIV-1 protease (HIV-1 PR) inhibitors can inhibit the in vitro and in vivo growth of Plasmodium falciparum. In this study, a series of chromone derivatives possessing HIV-1 PR inhibitory activity has been tested for antimalarial activity against P. falciparum (K1 multi-drug resistant strain). Chromone 15, the potent HIV-1 PR inhibitor (IC50 = 0.65 μM), was found to be the most potent antimalarial compound with IC50 = 0.95 μM while primaquine and tafenoquine showed IC50 = 2.41 and 1.95 μM, respectively. Molecular docking study of chromone compounds against plasmepsin II, an aspartic protease enzyme important in hemoglobin degradation, revealed that chromone 15 exhibited the higher binding affinity (binding energy = -13.24 kcal/mol) than the known PM II inhibitors. Thus, HIV-1 PR inhibitor in chromone series has the potential to be a new class of antimalarial agent.
Studies on gambogic acid (IV): Exploring structure-activity relationship with IκB kinase-beta (IKKβ)
Sun, Haopeng,Chen, Feihong,Wang, Xiaojian,Liu, Zongliang,Yang, Qian,Zhang, Xiaojin,Zhu, Jia,Qiang, Lei,Guo, Qinglong,You, Qidong
, p. 110 - 123 (2012/07/28)
Previously we have reported a series of gambogic acid's analogs and have identified a compound that possessed comparable in vitro growth inhibitory effect as gambogic acid. However, their target protein as well as the key pharmacophoric motifs on the target have not been identified yet. Herein we report that gambogic acid and its analogs inhibit the activity of IκB Kinase-beta (IKKβ) through suppressing the activation of TNFα/NF-κB pathway, which in turn induces A549 and U251 cell apoptosis. IKKβ can serve as one of gambogic acid's targets. The preparation of the compounds was carefully discussed in the article. Caged 4-oxa-tricyclo[4.3.1.03,7]dec-2-one xanthone, which was identified as the pharmacophoric scaffold, represents a promising therapeutic agent for cancer and useful probe against NF-κB pathway.
Synthesis, in vitro evaluation, and docking studies of novel chromone derivatives as HIV-1 protease inhibitor
Ungwitayatorn, Jiraporn,Wiwat, Chanpen,Samee, Weerasak,Nunthanavanit, Patcharawee,Phosrithong, Narumol
, p. 152 - 161 (2011/10/03)
Novel chromone derivatives with a benzopyran-4-one scaffold have been prepared by the one-pot cyclization reaction. The in vitro inhibitory activity of these new compounds towards HIV-1 protease have been evaluated using stop time HPLC method as the preliminary screening. The most potent compound, 7,8-dihydroxy-2-(3′-trifluoromethyl phenyl)-3-(3″- trifluoromethylbenzoyl)chromone (32), showed IC50 = 0.34 μM. The molecular docking study supported results from experimental activity testing and also provided structure-activity relationship of this series.
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
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, (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.
A METHOD FOR THE FACILE SYNTHESIS OF RING-A HYDROXYLATED FLAVONES
Cushman, Mark,Nagarathnam, Dhanapalan
, p. 6497 - 6500 (2007/10/02)
A general method for the facile synthesis of ring-A hydroxylated flavones is described.Treatment of the hydroxylated acetophenones 6a-d with enough lithium bis(trimethyl)silyl amide to deprotonate all of the phenols as well as to generate the lithium enolate of the ketone, followed by addition of the acid chlorides 7a-d, gave the 1,3-diketones 8a-g, which were cyclized to the desired products 9a-g in high yields.
SYNTHESE DE TRIHYDROXYPHENACYLIDENETRIPHENYLPHOSPHORANES UNE NOUVELLE VOIE D'ACCES AUX DIHYDROXYFLAVONES (CHRYSINE, ACACETINE...)
Le Floc'H, Yves,Lefeuvre, Martine
, p. 5503 - 5504 (2007/10/02)
An easy and convenient synthesys of two new trihydroxyphenacylidenetriphenylphosphoranes from phloroglucinol and pyrogallol is described.Some dihydroxyflavones are prepared by acylation of these ylids, intramolecular olefination and saponification of the two remaining ester groups.
