- Synthesis of new chalcone-based homoserine lactones and their antiproliferative activity evaluation
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Three series of new homoserine lactone analogs were efficiently synthesized starting from methionine and further evaluated for their antiproliferative activity against different cancer cell lines. Among these compounds, some of the chalcone containing compounds 6a-n showed acceptable antiproliferative activity against prostate cancer cells DU145 and PC-3 with the IC50 values less than 10 μM. Compounds 6c, 6e and 6h inhibited growth of DU145 and PC-3 cells at low micromolar levels with the IC50 values ranging from 3.0 to 5.0 μM, much more potent than natural OdDHL. Compound 6e concentration-dependently inhibited colony formation and cell migration of DU145 cells. A synergistic effect on the growth inhibition and the apoptosis of DU145 cells was observed when compound 6e was used in combination with TRAIL. OdDHL or 6e treatment concentration-dependently activated TRAIL death receptor DR5 which may account for the observed synergistic effect of 6e or OdDHL with TRAIL on the growth inhibition and cell apoptosis. Compound 6e also inhibited migration of DU145 cells in a time- and concentration-dependent manner. The data suggest that quorum sensing molecules OdDHL and 6e may improve the sensitivity of DU145 cells toward TRAIL via activating DR5, compound 6e may be used as a potential lead compound for developing new TRAIL receptor agonists.
- Yu, Bin,Liu, Haoyue,Kong, Xiaoyan,Chen, Xinli,Wu, Chunli
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p. 500 - 511
(2019/01/03)
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- A 2 - (2 - ethoxyphenoxy) bromo ethane industrial preparation method
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The invention discloses an industrial preparation method of 2-(2-ethoxyphenoxy)bromic ether, which belongs to the medicine synthesis field. The method comprises the following steps: taking 2-ethoxyphenoxy and 1,2-dibromoethane as raw materials, under existence of a phase-transfer catalyst, dropping a mild dilute aqueous alkali, and performing a substitution reaction, underpressure distillation and recrystallization to obtain 2-(2-ethoxyphenoxy)bromic ether. Through practical industrial production verification, the technology has the advantages of stable quality, mild reaction condition, safe and reliable operation and no three wastes pollution, 1,2-dibromoethane can be recycled and reused, the technical reappearance is good, preparation cost is low, and the industrial preparation method is reliable.
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Paragraph 0033; 0034; 0035
(2017/01/19)
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- Discovery of 1-aryloxyethyl piperazine derivatives as Kv1.5 potassium channel inhibitors (part I)
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Kv1.5 potassium channel is an efficacious and safe therapeutic target for the treatment of atrial fibrillation (AF), the most common arrhythmia that threatens human. Herein, by modifying the hit compound 7k from an in-house database, 48 derivatives were synthesized for the assay of their Kv1.5 inhibitory effects by whole cell patch clamp technique. Six compounds which showed better potency than the positive compound dronedarone were selected for the next evaluation of their drug-like properties. Compound 8 exhibited balanced solubility and permeability. It also showed acceptable pharmacodynamics profile with very low acute toxicity. Taking all these data into account, compound 8 can serve as a promising lead for the development of novel therapeutic agent for the treatment of AF.
- Guo, Xiaoke,Ma, Xianglei,Yang, Qian,Xu, Jing,Huang, Lu,Jia, Jianmin,Shan, Jiaojiao,Liu, Li,Chen, Weilin,Chu, Hongxi,Wei, Jinlian,Zhang, Xiaojin,Sun, Haopeng,Tang, Yiqun,You, Qidong
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supporting information
p. 89 - 94
(2014/06/09)
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