475576-83-1Relevant academic research and scientific papers
Design, synthesis and characterization of potent microtubule inhibitors with dual anti-proliferative and anti-angiogenic activities
Zhang, Huijun,Fang, Xiong,Meng, Qian,Mao, Yujia,Xu, Yan,Fan, Tingting,An, Jing,Huang, Ziwei
, p. 380 - 396 (2018/08/17)
Microtubule has been an important target for anticancer drug development. Here we report the discovery and characterization of a series of fused 4-aryl-4H-chromene-based derivatives as highly potent microtubule inhibitors. Among a total of 37 derivatives synthesized, 23 exhibited strong in vitro anti-proliferative activities against A375 human melanoma cells. The relationship between the biological activities of these microtubule inhibitors and their chemical structure variations was analyzed. Studies of compounds 27a, 19a and 9a in parallel with colchicine as the positive control compound in a panel of biological assays revealed that these compounds blocked cell cycle progression, increased apoptosis, and inhibited HUVEC capillary tube formation at low nanomolar concentrations. The most potent compound 27a was also tested in eight additional cancer cell lines besides A375 cells and two non-cancer cells and showed potent and selective activity on these cancer cells. To understand the molecular and structure mechanism of action of these compounds, tubulin polymerization and molecular docking studies were carried out for 27a as the representative. The results were consistent with the mechanism by which 27a interacts with the colchicine binding site on tubulin and disrupts tubulin polymerization. With potent dual actions of microtubule destabilization and vascular disruption described above, this small molecule can serve as a valuable research probe of the function and role of microtubules in human diseases and promising lead for developing new therapeutic agents.
SUBSTITUTED 4-ARYL-CHROMENE AS ACTIVATOR OF CASPASES AND INDUCER OF APOPTOSIS AND AS ANTIVASCULAR AGENT AND THE USE THEREOF
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Page/Page column 35, (2008/06/13)
The present invention is directed to a substituted 4H-chromene represented by the Formula 1R, substantially free from the corresponding (S)-stereoisomer: The present invention also relates to the discovery that compound 1R, substantially free from the cor
Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 2. Structure-activity relationships of the 7- and 5-, 6-, 8-positions
Kemnitzer, William,Kasibhatla, Shailaja,Jiang, Songchun,Zhang, Hong,Zhao, Jianghong,Jia, Shaojuan,Xu, Lifen,Crogan-Grundy, Candace,Denis, Real,Barriault, Nancy,Vaillancourt, Louis,Charron, Sylvie,Dodd, Jennifer,Attardo, Giorgio,Labrecque, Denis,Lamothe, Serge,Gourdeau, Henriette,Tseng, Ben,Drewe, John,Cai, Sui Xiong
, p. 4745 - 4751 (2007/10/03)
As a continuation of our efforts to discover and develop the apoptosis inducing 4-aryl-4H-chromenes as novel anticancer agents, we explored the SAR of 4-aryl-4H-chromenes with modifications at the 7- and 5-, 6-, 8-positions. It was found that a small hydr
Substituted 4H-chromenes and analogs as activators of caspases and inducers of apoptosis and the use thereof
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, (2008/06/13)
The present invention is directed to substituted 4H-chromenes and analogs thereof, represented by the general Formula I: 1wherein R1-R5, A, Y and Z are defined herein. The present invention also relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.
