16290-50-9Relevant academic research and scientific papers
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).
Design and synthesis of novel Flavone-based histone deacetylase inhibitors antagonizing activation of STAT3 in breast cancer
Wei, Mingming,Xie, Maodun,Zhang, Zhen,Wei, Yujiao,Zhang, Juan,Pan, Hongli,Li, Benlong,Wang, Jingjing,Song, Yang,Chong, Chuangke,Zhao, Rui,Wang, Jiefu,Yu, Li,Yang, Guang,Yang, Cheng
, (2020/08/21)
Histone deacetylases (HDACs) inhibitors have demonstrated a great clinical achievement in hematological malignancies. However, the efficacy of HDACs inhibitors in treating solid tumors remains limited due to the complicated tumor microenvironment. In this study, we designed and synthesized a class of novel HDACs inhibitors based on the structure of flavones and isoflavones, followed by biological evaluation. To be specific, a lead compound 15a was discovered with strong anti-proliferative effects on a variety of solid tumor cells, especially for breast cancer cells with resistance to SAHA. Studies demonstrated that 15a could significantly inhibit the activity of HDAC 1, 2, 3 (class I) and 6 (class IIB), leading to a dose-dependent accumulation of acetylated histones and α-Tubulin, cell cycle arrest (G1/S phase) and apoptosis in breast cancer cells. Furthermore, the lead compound 15a could also antagonize the activation of STAT3 induced by HDACs inhibition in some breast cancer cells, which further reduced the level of pro-survive proteins in tumor cells and enhanced anti-tumor activity regulated by STAT3 signaling in vivo. Overall, our findings demonstrated that the novel compound 15a might be a HDACs inhibitor candidate, which could be used as promising chemotherapeutic agent for breast cancer.
Design, synthesis, and characterization of novel apigenin analogues that suppress pancreatic stellate cell proliferation in vitro and associated pancreatic fibrosis in vivo
Chen, Haijun,Mrazek, Amy A.,Wang, Xiaofu,Ding, Chunyong,Ding, Ye,Porro, Laura J.,Liu, Huiling,Chao, Celia,Hellmich, Mark R.,Zhou, Jia
, p. 3393 - 3404 (2014/06/23)
Accumulating evidence suggests that activated pancreatic stellate cells (PSC) play an important role in chronic pancreatitis (CP), and inhibition of the activated PSC is considered as a potential strategy for the treatment and prevention of CP. Herein, we disclose our findings that apigenin and its novel analogues suppress the proliferation and induce apoptosis in PSC, which reduce the PSC-mediated fibrosis in CP. Chemical modifications of apigenin have been directed to build a focused library of O-alkylamino-tethered apigenin derivatives at 4′-O position of the ring C with the attempt to enhance the potency and drug-like properties including aqueous solubility. A number of compounds such as 14, 16, and 24 exhibited potent antiproliferative effects as well as improved aqueous solubility. Intriguingly, apigenin, new analogues 23 and 24 displayed significant efficacy to reduce pancreatic fibrosis even at a low dose of 0.5 mg/kg in our proof-of-concept study using a preclinical in vivo mouse model of CP.
First total synthesis of protoapigenone and its analogues as potent cytotoxic agents
Lin, An-Shen,Nakagawa-Goto, Kyoko,Chang, Fang-Rong,Yu, Donglei,Morris-Natschke, Susan L.,Wu, Chin-Chung,Chen, Shu-Li,Wu, Yang-Chang,Lee, Kuo-Hsiung
, p. 3921 - 3927 (2008/02/10)
Protoapigenone (1), isolated from Thelypteris torresiana, previously showed significant cytotoxic activity against five human cancer cell lines. In a continued structure-activity relationship study, the first total synthesis and modification of 1 were ach
