3754-52-7Relevant academic research and scientific papers
A novel Apigenin derivative suppresses renal cell carcinoma via directly inhibiting wild-type and mutant MET
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
, (2021)
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.
Flavone derivative and application thereof
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, (2021/02/24)
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.
Synthesis of new biheterocycles by a one-pot sonogashira coupling reaction
Deodhar, Mandar,Black, David Stc.,Kumar, Naresh
, p. 1489 - 1501 (2011/05/14)
Halogenated flavones, isoflavones and indoles were subjected to a one-pot Sonogashira coupling reaction to generate a series of new biheterocyclic compounds. The methodology can be readily adapted to the synthesis of a wide variety of substituted biheterocycles. The Japan Institute of Heterocyclic Chemistry.
Total synthesis of robustaflavone, a potential anti-hepatitis B agent
Zembower, David E.,Zhang, Heping
, p. 9300 - 9305 (2007/10/03)
Robustaflavone, a naturally occurring compound, is an inhibitor of hepatitis B virus replication in vitro. Robustaflavone is a biflavanoid composed of two units of apigenin (5,7,4'-trihydroxyflavone) joined via a biaryl linkage between the 6-position of one unit and the 3'-position of the other (I6,II3'-biapigenin). The natural material was isolated from the seed- kernels of Rhus succedanea. To provide ready access to sufficient quantities of material for continued biological studies, as well as to provide a general route for the preparation of structural analogues, a total synthesis of robustaflavone was pursued. The total synthesis was approached by constructing apigenin ethers containing functionalities at the 6- and 3'- positions which could be cross-coupled using transition metal catalysis. Key steps of the synthesis included development of a regioselective iodination of an apigenin derivative at the 6-position. Also key was the formation of an apigenin 3'-boronate using a palladium-catalyzed exchange of the corresponding 3'-iodide with a diboron reagent. Finally, identification of appropriate reaction conditions for Suzuki coupling to form the sterically congested 6-3''' biaryl bond of robustaflavone provided access to the desired biflavanoid system. This work represents the first total synthesis of robustaflavone.
