446866-87-1Relevant articles and documents
Design, synthesis and biological evaluation of dimethyl cardamonin (DMC) derivatives as P-glycoprotein-mediated multidrug resistance reversal agents
Liu, Jianwen,Ma, Lei,Shi, Ximeng,Yin, Huanhuan,Zhao, Yuyu,Zhou, Licheng
, p. 1270 - 1282 (2020/10/06)
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.
Design, synthesis and biological evaluation of chalcones as reversers of P-glycoprotein-mediated multidrug resistance
Yin, Huanhuan,Dong, Jingjing,Cai, Yingchun,Shi, Ximeng,Wang, Hao,Liu, Guixia,Tang, Yun,Liu, Jianwen,Ma, Lei
, p. 350 - 366 (2019/07/19)
Overexpression of P-glycoprotein (P-gp) is one of the major causes for multidrug resistance (MDR), which has become a major obstacle in cancer therapy. One hopeful approach to reverse the MDR is to develop inhibitors of P-gp in expression and/or function. Here, we designed and synthesized a series of chalcone derivatives as P-gp inhibitors and evaluated their potential reversal activities against MDR. Among them, the most active compound MY3 had little intrinsic cytotoxicity and showed the highest activity (RF = 50.19) in reversing DOX resistance in MCF-7/DOX cells. Further studies demonstrated that MY3 could increase intracellular accumulation of DOX and inhibit expression of P-gp at mRNA and protein levels. More importantly, MY3 significantly enhanced the efficacy of DOX against the tumor xenografts bearing MCF-7/DOX cells with the precondition of unchanged body weight. Therefore, MY3 might represent a promising lead to develop MDR reversal agents for cancer chemotherapy.
Nickel-Catalyzed Decarboxylation of Aryl Carbamates for Converting Phenols into Aromatic Amines
Nishizawa, Akihiro,Takahira, Tsuyoshi,Yasui, Kosuke,Fujimoto, Hayato,Iwai, Tomohiro,Sawamura, Masaya,Chatani, Naoto,Tobisu, Mamoru
supporting information, p. 7261 - 7265 (2019/05/16)
Herein, we describe a new catalytic approach to accessing aromatic amines from an abundant feedstock, namely phenols. The most reliable catalytic method for converting phenols to aromatic amines uses an activating group, such as a trifluoromethane sulfonyl group. However, this activating group is eliminated as a leaving group during the amination process, resulting in significant waste. Our nickel-catalyzed decarboxylation reaction of aryl carbamates forms aromatic amines with carbon dioxide as the only byproduct. As this amination proceeds in the absence of free amines, a range of functionalities, including a formyl group, are compatible. A bisphosphine ligand immobilized on a polystyrene support (PS-DPPBz) is key to the success of this reaction, generating a catalytic species that is significantly more active than simple nonsupported variants.
Base Catalysis Enables Access to α,α-Difluoroalkylthioethers
Orsi, Douglas L.,Easley, Brandon J.,Lick, Ashley M.,Altman, Ryan A.
, p. 1570 - 1573 (2017/04/13)
A nucleophilic addition reaction of aryl thiols to readily available β,β-difluorostyrenes provides α,α-difluoroalkylthioethers. The reaction proceeds through an unstable anionic intermediate, prone to eliminate fluoride and generate α-fluorovinylthioethers. However, the use of base catalysis overcomes the facile β-fluoride elimination, generating α,α-difluoroalkylthioethers in excellent yields and selectivities.
Synthesis and characterization of Sant-75 derivatives as Hedgehog-pathway inhibitors
Che, Chao,Li, Song,Yang, Bo,Xin, Shengchang,Yu, Zhixiong,Shao, Taofeng,Tao, Chuanye,Lin, Shuo,Yang, Zhen
scheme or table, p. 841 - 849 (2012/07/28)
Sant-75 is a newly identified potent inhibitor of the hedgehog pathway. We designed a diversity-oriented synthesis program, and synthesized a series of Sant-75 analogues, which lays the foundation for further investigation of the structure-activity relationship of this important class of hedgehog-pathway inhibitors.
Arylcyanoacrylamides as inhibitors of the Dengue and West Nile virus proteases
Nitsche, Christoph,Steuer, Christian,Klein, Christian D.
experimental part, p. 7318 - 7337 (2012/01/05)
The 3-aryl-2-cyanoacrylamide scaffold was designed as core pharmacophore for inhibitors of the Dengue and West Nile virus serine proteases (NS2B-NS3). A total of 86 analogs was prepared to study the structure-activity relationships in detail. Thereby, it turned out that the electron density of the aryl moiety and the central double bond have a crucial influence on the activity of the compounds, whereas the influence of substituents of the amide residue is less relevant. The para-hydroxy substituted analog was found to be the most potent inhibitor in this series with a Ki-value of 35.7 μM at the Dengue and 44.6 μM at the West Nile virus protease. The aprotinin competition assay demonstrates a direct interaction of the inhibitor molecule with active centre of the Dengue virus protease. The target selectivity was studied in a counterscreen with thrombin and found to be 2.8:1 in favor of DEN protease and 2.3:1 in favor of WNV protease, respectively.
Novel Compounds
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Page/Page column 70, (2008/06/13)
There is provided a compound of formula (I): processes for the manufacture thereof, pharmaceutical compositions thereof and uses in therapy.
