1775-97-9Relevant academic research and scientific papers
Synthesis and acetylcholinesterase inhibitory activity of Mannich base derivatives flavokawain B
Liu, Hao-Ran,Huang, Xue-Qin,Lou, Ding-Hui,Liu, Xian-Jun,Liu, Wu-Kun,Wang, Qiu-An
, p. 4749 - 4753 (2014)
A novel series of flavokawain B derivatives, chalcone Mannich bases (4-10) were designed, synthesized, characterized, and evaluated for the inhibition activity against acetylcholinesterase (AChE). Biological results revealed that four compounds displayed potent activities against AChE with IC50values below 20 μM. Moreover, the most promising compound 8 was 2-fold more active than rivastigmine, a well-known AChE inhibitor. The log P values of 4-10 were around 2 which indicated that they were sufficiently lipophilic to pass blood brain barriers in vivo. Enzyme kinetic study suggested that the inhibition mechanism of compound 8 was a mixed-type inhibition. Meanwhile, the molecular docking showed that this compound can both bind with the catalytic site and the periphery of AChE.
Chalcone methoxy derivatives exhibit antiproliferative and proapoptotic activity on canine lymphoma and leukemia cells
?uz?ny, Mateusz,Henklewska, Marta,Janeczko, Tomasz,Koz?owska, Ewa,Obmińska-Mrukowicz, Bozena,Pawlak, Aleksandra,Suárez, Beatriz Hernández
, (2020)
Chalcones are interesting candidates for anti-cancer drugs due to the ease of their synthesis and their extensive biological activity. The study presents antitumor activity of newly synthesized chalcone analogues with a methoxy group on a panel of canine lymphoma and leukemia cell lines. The antiproliferative effect of the 20-hydroxychalcone and its methoxylated derivatives was evaluated in MTT assay after 48 h of treatment in different concentrations. The proapoptotic activity was studied by cytometric analysis of cells stained with Annexin V/FITC and propidium iodide and by measure caspases 3/7 and 8 activation. The DNA damage was evaluated by Western blot analysis of phosphorylated histone H2AX. The new compounds had selective antiproliferative activity against the studied cell lines, the most effective were the 20-hydroxy-200,500-dimethoxychalcone and 20-hydroxy-40,60-dimethoxychalcone. 20-Hydroxychalcone and the two most active derivatives induced apoptosis and caspases participation, but some percentage of necrotic cells was also observed. Comparing phosphatidylserine externalization after treatment with the different compounds it was noted that the addition of two methoxy groups increased the proapoptotic potential. The most active compounds triggered DNA damage even in the cell lines resistant to chalcone-induced apoptosis. The results confirmed that the analogues could have anticancer potential in the treatment of canine lymphoma or leukemia.
An efficient synthesis of chrysin
Liu, Man,Zhang, Ji,Yang, Jian,Yang, Bo,Cui, Wei
, p. 134 - 136 (2014)
Two routes for the synthesis of the flavones chrysin are described. In the first 1,3,5-trimethoxybenzene was converted to 2-hydroxy-4,6- dimethoxyacetophenone and then by condensation with benzaldehyde to 2′-hydroxy-4′,6′-dimethoxychalcone. The latter was cyclised with iodine and demethylated with pyridine hydrochloride to form chrysin in 53% overall yield. In the second route, 1,3,5-trimethoxybenzene was acylated with cinnamic acid to form the chalcone which was then converted to chrysin in 30.7% overall yield.
Development of a concise synthesis of the flavonoid chrysin
Wang, Qian,Cui, Wei,Yang, Jian,Yang, Bo
, p. 300 - 302 (2015)
Two novel routes for the synthesis of the flavonoid chrysin are described. In the first, 3,5-dimethoxyphenol (taxicatigenin) was converted to 2-hydroxy-4,6-dimethoxyacetophenone and then by condensation with benzaldehyde to 2'-hydroxy-4',6'-dimethoxychalcone. The latter was cyclised with iodine and demethylated with pyridine hydrochloride to form chrysin in 50% overall yield. In the second route, taxicatigenin was acylated with cinnamoyl chloride to form a chalcone under special conditions. This was then converted to chrysin in 42% and 56% overall yield, respectively. Several disadvantages of previous syntheses like long reaction time, tedious work-up and low overall yield have been overcome.
Melanogenic inhibition and toxicity assessment of flavokawain A and B on B16/F10 melanoma cells and zebrafish (Danio rerio)
Abdul Bahari, Mohammad Nazri,Ahmad, Syahida,Akhtar, Muhammad Nadeem,Balia Yusof, Zetty Norhana,Latif, Naimah,Md Razip, Nurliyana Najwa,Mohd Ma’in, Farah Idayu,Sakeh, Nurshafika Mohd
, (2020)
Excessive production of melanin implicates hyperpigmentation disorders. Flavokawain A (FLA) and flavokawain B (FLB) have been reported with anti-melanogenic activity, but their melanogenic inhibition and toxicity effects on the vertebrate model of zebrafish are still unknown. In the present study, cytotoxic as well as melanogenic effects of FLA and FLB on cellular melanin content and tyrosinase activity were evaluated in α-MSH-induced B16/F10 cells. Master regulator of microphthalmia-associated transcription factor (Mitf) and the other downstream melanogenic-related genes were verified via quantitative real time PCR (qPCR). Toxicity assessment and melanogenesis inhibition on zebrafish model was further observed. FLA and FLB significantly reduced the specific cellular melanin content by 4.3-fold and 9.6-fold decrement, respectively in α-MSH-induced B16/F10 cells. Concomitantly, FLA significantly reduced the specific cellular tyrosinase activity by 7-fold whilst FLB by 9-fold. The decrement of melanin production and tyrosinase activity were correlated with the mRNA suppression of Mitf which in turn down-regulate Tyr, Trp-1 and Trp-2. FLA and FLB exhibited non-toxic effects on the zebrafish model at 25 and 6.25 μM, respectively. Further experiments on the zebrafish model demonstrated successful phenotype-based depigmenting activity of FLA and FLB under induced melanogenesis. To sum up, our findings provide an important first key step for both of the chalcone derivatives to be further studied and developed as potent depigmenting agents.
Biotransformation of 5,7-Methoxyflavones by Selected Entomopathogenic Filamentous Fungi
?u?ny, Mateusz,Tronina, Tomasz,Koz?owska, Ewa,Kostrzewa-Sus?ow, Edyta,Janeczko, Tomasz
, p. 3879 - 3886 (2021/05/04)
5,7-Dimethoxyflavone, a chrysin derivative, occurs in many plants and shows very low toxicity, even at high doses. On the basis of this phenomenon, we biotransformed a series of methoxy-derivatives of chrysin, apigenin, and tricetin obtained by chemical synthesis. We used entomopathogenic fungal strains with the confirmed ability of simultaneous hydroxylation/demethylation and glycosylation of flavonoid compounds. Both the amount and the place of attachment of the methoxy group influenced the biotransformation rate and the product's amount nascent. Based on product and semi-product structures, it can be concluded that they are the result of cascading transformations. Only in the case of 5,7,3′,4′,5′-pentamethoxyflavone, the strains were able to attach a sugar molecule in place of the methoxy substituent to give 3′-O-β-d-(4″-O-methylglucopyranosyl)-5,7,4′,5′-tetramethoxyflavone. However, we observed the tested strains' ability to selectively demethylate/hydroxylate the carbon C-3′ and C-4′ of ring B of the substrates used. The structures of four hydroxyl-derivatives were determined: 4′-hydroxy-5,7-dimethoxyflavone, 3′-hydroxy-5,7-dimethoxyflavone, 3′-hydroxy-5,7,4′,5′-tetramethoxyflavone, and 5,7-dimethoxy-3′,4′-dihydroxyflavone (5,7-dimethoxy-luteolin).
Discovery of polymethoxyflavones as potential cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and phosphodiesterase 4B (PDE4B) inhibitors
Hamzah, Ahmad Sazali,Md Idris, Muhd Hanis,Mohd Amin, Siti Norhidayah,Mohd Amin, Siti Norhidayu,Salleh, Mohd Zaki,Selvaraj, Manikandan,Shaameri, Zurina,Teh, Lay Kek,Wibowo, Agustono,Zakaria, Zainul Amiruddin
, (2021/08/06)
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed to treat inflammatory-related diseases, pain and fever. However, the prolong use of traditional NSAIDs leads to undesirable side effects such as gastric, ulceration, and renal toxicity due to lack of selectivity toward respective targets for COX-2, 5-LOX, and PDE4B. Thus, targeting multiple sites can reduce these adverse effects of the drugs and increase its potency. A series of methoxyflavones (F1–F5) were synthesized and investigated for their anti-inflammatory properties through molecular docking and inhibition assays. Among these flavones, only F2 exhibited selectivity toward COX-2 (Selectivity Index, SI: 3.90, COX-2 inhibition: 98.96 ± 1.47%) in comparison with celecoxib (SI: 7.54, COX-2 inhibition: 98.20 ± 2.55%). For PDEs, F3 possessed better selectivity to PDE4B (SI: 4.67) than rolipram (SI: 0.78). F5 had the best 5-LOX inhibitory activity among the flavones (33.65 ± 4.74%) but less than zileuton (90.81 ± 0.19%). Docking analysis indicated that the position of methoxy group and the substitution of halogen play role in determining the bioactivities of flavones. Interestingly, F1–F5 displayed favorable pharmacokinetic profiles and acceptable range of toxicity (IC50>70 μM) in cell lines with the exception for F1 (IC50: 16.02 ± 1.165 μM). This study generated valuable insight in designing new anti-inflammatory drug based on flavone scaffold. The newly synthesized flavones can be further developed as future therapeutic agents against inflammation.
Chalcone derivative and application thereof
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Paragraph 0014-0016, (2021/07/01)
The invention discloses a chalcone derivative and application thereof. The chemical structure of the chalcone derivative is shown as a formula (a) or a formula (b). The chalcone derivative can effectively inhibit proliferation of tumor cells, and a novel lead compound is provided for development of antitumor drugs.
A novel one-pot synthesis of flavones
Chang, Meng-Yang,Tsai, Min-Chen,Lin, Chun-Yi
, p. 11655 - 11662 (2021/03/31)
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.
Novel chromenone derivatives having substituted biphenyl group and a pharmaceutical composition for prevention or treatment of allergic diseases compring the same
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Paragraph 0076-0083, (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
