- Total Synthesis of Mulberry Diels-Alder-Type Adducts Kuwanons G and H
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Mulberry Diels-Alder-type adducts (MDAAs) are a group of rare natural polyphenols biosynthetically derived from [4 + 2]-cycloaddition of chalcones and dehydroprenylphenols. In this study, kuwanons G (1) and H (2), two bioactive MDAAs with unique dehydroprenylflavonoid dienes, were totally synthesized for the first time in a biomimetic manner. The key features of the convergent route include the use of the Baker-Venkataraman rearrangement, alkylation of β-diketone, intramolecular cyclization, and Suzuki-Miyaura coupling to achieve the subunit diene.
- Luo, Si-Yuan,Tang, Zhuo-Ya,Li, Qingjiang,Weng, Jiang,Yin, Sheng,Tang, Gui-Hua
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p. 4786 - 4793
(2021/04/06)
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- Discovery of polymethoxyflavones as potential cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and phosphodiesterase 4B (PDE4B) inhibitors
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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.
- 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
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- A novel Apigenin derivative suppresses renal cell carcinoma via directly inhibiting wild-type and mutant MET
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MET, the receptor of hepatocyte growth factor (HGF), is a driving factor in renal cell carcinoma (RCC) and also a proven drug target for cancer treatment. To improve the activity and to investigate the mechanisms of action of Apigenin (APG), novel derivatives of APG with improved properties were synthesized and their activities against Caki-1 human renal cancer cell line were evaluated. It was found that compound 15e exhibited excellent potency against the growth of multiple RCC cell lines including Caki-1, Caki-2 and ACHN and is superior to APG and Crizotinib. Subsequent investigations demonstrated that compound 15e can inhibit Caki-1 cell proliferation, migration and invasion. Mechanistically, 15e directly targeted the MET kinase domain, decreased its auto-phosphorylation at Y1234/Y1235 and inhibited its kinase activity and downstream signaling. Importantly, 15e had inhibitory activity against mutant MET V1238I and Y1248H which were resistant to approved MET inhibitors Cabozantinib, Crizotinib or Capmatinib. In vivo tumor graft study confirmed that 15e repressed RCC growth through inhibition of MET activation. These results indicate that compound 15e has the potential to be developed as a treatment for RCC, and especially against drug-resistant MET mutations.
- Li, Jing,Tan, Guishan,Cai, Yabo,Liu, Ruihuan,Xiong, Xiaolin,Gu, Baohua,He, Wei,Liu, Bing,Ren, Qingyun,Wu, Jianping,Chi, Bo,Zhang, Hang,Zhao, Yanzhong,Xu, Yangrui,Zou, Zhenxing,Kang, Fenghua,Xu, Kangping
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- Flavone derivative and application thereof
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The invention discloses a flavone derivative and the application thereof. The flavone derivative is a compound with multiple target points and multiple functions for preventing Alzheimer's diseases. The compound and a pharmaceutical salt thereof can be applied to preparation of corresponding medicines, and the compound can be also applied to antioxidants, multiple enzyme inhibitors and metal chelating agents.
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- Green synthesis of novel chalcone and coumarin derivatives via Suzuki coupling reaction
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Chalcones and coumarins are important naturally occurring plant constituents and display a wide range of pharmacological and biological activities. In an environmentally benign approach, synthesis of biphenyl chalcone and coumarin derivatives was successfully accomplished via Suzuki coupling by using PEG-400 as a solvent under microwave irradiation. Salient feature of this methodology includes: short reaction time, good to excellent yields, and prominent tolerance of different functional groups.
- Vieira, Lucas C.C.,Paix?o, Márcio Weber,Corrêa, Arlene G.
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supporting information; experimental part
p. 2715 - 2718
(2012/07/14)
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- Regioselective synthesis of prenylisoflavones. Syntheses of allolicoisoflavone A, 2,3-dehydrokievitone, and related compounds
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The palladium-catalyzed coupling reaction of 2',4',5,7- tetrakis(benzyloxy)-5'-iodolsoflavone (12), synthesized from the 5- iodochalcone 9, with 2-methyl-3-butyn-2-ol gave the corresponding 5'-(3- hydroxy-3-methyl-1-butynyl)isoflavone 13. The catalytic hydrogenation of 13 gave 2',4',5,7-tetrahydroxy-5'-(3-hydroxy-3-methylbutyl)isoflavone (2). Dehydration of the benzoate 14 of 2 afforded a mixture of 5'-(3-methyl-2- butenyl)isoflavone 15 and the isomer 5'-(3-methyl-3-butenyl)isoflavone 16. The separation of 15 was accomplished by a treatment of the mixture (15 and 16) with mercury(II) nitrate. Hydrolysis of 15 afforded 2',4',5,7- tetrahydroxy-5'-prenylisoflavone (allolicoisoflavone A) (1). In a similar manner, 2',4',5,7-tetrahydroxy-8-prenylisoflavone (2,3-dehydrokievitone) (3) and 2',4',5,7-tetrahydroxy-8-(3-hydroxy-3-methylbutyl)isoflavone (2,3- dehydrokievitone hydrate) (4) were synthesized from the corresponding 8- iodoisoflavone 22. The tetramethyl ether 5 of 3 was also prepared from the 8- iodotetramethoxyisoflavone 32.
- Tsukayama, Masao,Li, He,Tsurumoto, Ken,Nishiuchi, Masaki,Kawamura, Yasuhiko
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p. 2673 - 2680
(2007/10/03)
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