- Anti‐melanogenic properties of velutin and its analogs?
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Velutin, one of the flavones contained in natural plants, has various beneficial activities, such as skin whitening, as well as anti‐inflammatory, anti‐allergic, antioxidant, and antimicrobial activities. However, the relationship between the structure of velutin and its anti‐melanogenesis activity is not yet investigated. In this study, we obtained 12 velutin derivatives substituted at C5, C7, C3′, and C4′ of the flavone backbone with hydrogen, hydroxyl, and methoxy functionalities by chemical synthesis, to perform SAR analysis of velutin structural analogues. The SAR study revealed that the substitution of functional groups at C5, C7, C3′, and C4′ of the flavone backbone affects biological activities related to melanin synthesis. The coexistence of hydroxyl and methoxy at the C5 and C7 position is essential for inhibiting tyrosinase activity. However, 1,2‐diol compounds substituted at C3′ and C4′ of flavone backbone induce apoptosis of melanoma cells. Further, substitution at C3′ and C4′ with methoxy or hydrogen is essential for inhibiting melanogenesis. Thus, this study would be helpful for the development of natural‐derived functional materials to regulate melanin synthesis.
- Choe, Jung-Won,Heo, Hee-Young,Jung, Se-Hui,Kim, Jaehyun,Lee, Kooyeon
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- Design and synthesis of novel Flavone-based histone deacetylase inhibitors antagonizing activation of STAT3 in breast cancer
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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.
- 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
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- Design, synthesis and biological evaluation of dimethyl cardamonin (DMC) derivatives as P-glycoprotein-mediated multidrug resistance reversal agents
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Background: P-glycoprotein (P-gp) has been regarded as an important factor in the multidrug resistance (MDR) of tumor cells within the last decade, which can be solved by inhibiting P-gp to reverse MDR. Thus, it is an effective strategy to develop inhibitor of P-gp. Objective: In this study, the synthesis of a series of derivatives had been carried out by bioisosterism design on the basis of Dimethyl Cardamonin (DMC). Subsequently, we evaluated their reversal activities as potential P-glycoprotein (P-gp)-mediated Multidrug Resistance (MDR) agents. Methods: Dimethyl cardamonin derivatives were synthesized from acetophenones and the corresponding benzaldehydes in the presence of 40% KOH by Claisen-Schmidt reaction. Their cytotoxicity and reversal activities in vitro were assessed with MTT. Moreover, the compound B4 was evaluated by Doxorubicin (DOX) accumulation, Western blot and wound-healing assays deeply. Results and Discussion: The results showed that compounds B2, B4 and B6 had the potency of MDR reversers with little intrinsic cytotoxicity. Meanwhile, these compounds also demonstrated the capability to inhibit MCF-7 and MCF-7/DOX cells migration. Besides, the most compound B4 was selected for further study, which promoted the accumulation of DOX in MCF-7/DOX cells and inhibited the expressionof P-gp at protein levels. Conclusion: The above findings may provide new insights for the research and development of P-gp-mediated MDR reversal agents.
- Liu, Jianwen,Ma, Lei,Shi, Ximeng,Yin, Huanhuan,Zhao, Yuyu,Zhou, Licheng
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p. 1270 - 1282
(2020/10/06)
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- Synthesis method of isolicoflavonol
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The invention provides a synthesis method of isolicoflavonol, which comprises the following steps: carrying out condensation reaction on 2,4-O-R1(protective group, the same below)-6-hydroxyacetophenone and 4-O-R2(protective group, the same below)-benzaldehyde to generate 2',4'-O-R1-6'-hydroxy-4-O-R2-chalcone; oxidizing the chalcone to generate flavonol; carrying out selective protection on 3-OH ofthe flavonol to obtain 3,5,7-O-R1-4'-O-R2-flavonol; removing the protecting group R2 from the 3,5,7-O-R1-4'-O-R2-flavonol to obtain 3,5,7-O-R1-4'-hydroxyflavonol; carrying out 1,1-dimethylpropargyl reaction on the 4,4'-OH site to obtain 3,5,7-O-R1-4'-O-(1',1''-dimethyl propargyl)flavonol; carrying out partial hydrogenation on the alkynyl of the 3,5,7-O-R1-4'-O-(1',1''-dimethyl propargyl)flavonolunder the action of a catalyst to obtain 3,5,7-O-R1-4'-O-(1',1''-dimethylpropenyl)flavonol and carrying out Claisen rearrangement on the 3,5,7-O-R1-4'-O-(1',1''-dimethylpropenyl)flavonol to obtain 3,5,7-O-R1-isolicoflavonol, and removing the protecting group R1 from the 3,5,7-O-R1-isolicoflavonol to obtain the isolicoflavonol.
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Paragraph 0111; 0194-0201
(2020/12/29)
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- First total synthesis of protoapigenone and its analogues as potent cytotoxic agents
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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
- 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
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p. 3921 - 3927
(2008/02/10)
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- Synthesis of 2-Benzylidene-3(2H)-benzofuran-3-ones (Aurones) by Oxidation of 2'-Hydroxychalcones with Mercury(II) Acetate
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The reaction of 2'-hydroxychalcones with mercury(II) acetate in acetic acid gives predominantly 2-benzylidene-3(2H)-benzofuran-3-ones (aurones) in 28-62 percent yield accompanied by flavonones in 5-21 percent yield.
- Sekizaki, Haruo
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p. 1407 - 1409
(2007/10/02)
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- PHENOLIC CONSTITUENTS FROM SEEDS OF COPTIS JAPONICA VAR. DISSECTA
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In addition to coumarinolignans (cleomiscosin A and aquillochin) and 7,4'-dihydroxy-5-methoxyflavanone, a new dihydrochalcone, 2',4,4'-trihydroxy-6'-methoxydihydrochalcone, was isolated from the seeds of Coptis japonica var. dissecta.The structure of the dihydrochalcone was confirmed by comparison with relevant synthetic samples. - Key Word Index: Coptis japonica var. dissecta; Ranunculaceae; cleomiscosin A; aquillochin; 2',4,4'-trihydroxy-6'-methoxydihydrochalcone; 7,4'-dihydroxy-5-methoxyflavanone.
- Mizuno, Mizuo,Kojima, Hiroyuki,Tanaka, Toshijuki,Iinuma, Munekazu,Kimura, Rie,et al.
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p. 2071 - 2074
(2007/10/02)
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