当前位置：
X-MOL 学术
›
J. Med. Chem.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Synthesis and Biological Evaluation of Selenium-Containing 4-Anilinoquinazoline Derivatives as Novel Antimitotic Agents
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2018-03-06 00:00:00 , DOI: 10.1021/acs.jmedchem.8b00128 Baijiao An 1 , Bo Wang 1 , Jinhui Hu 1 , Shaoyu Xu 1 , Ling Huang 1 , Xingshu Li 1 , Albert S. C. Chan 1
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2018-03-06 00:00:00 , DOI: 10.1021/acs.jmedchem.8b00128 Baijiao An 1 , Bo Wang 1 , Jinhui Hu 1 , Shaoyu Xu 1 , Ling Huang 1 , Xingshu Li 1 , Albert S. C. Chan 1
Affiliation
|
Twenty-eight novel selenium-containing 4-anilinoquinazoline derivatives were designed, synthesized, and evaluated as antiproliferative agents. Most of them had significant in vitro activities, particularly for compounds 23a, 25a, and 25d, which also exhibited the most potent antitumor activities against cisplatin-resistant cell lines and the doxorubicin-resistant cell lines, good selectivity toward normal cells, and obvious inhibitory effect on migration of A549 cell lines. Further mechanistic studies revealed that 23a, 25a, and 25d induce G2/M phase arrest and apoptosis in A549 cells, which was associated with a collapse of the mitochondrial membrane potential, alterations in the expression of some cell cycle-related and apoptosis-related proteins, and increasing the intracellular ROS level. Finally, compounds 23a, 25a, and 25d also effectively inhibited the tumor growth in the A549 xenograft model without obvious hints of toxicity. Taken together, these in vitro and in vivo results suggest that 23a, 25a, and 25d may be promising microtubule-stabilizing agents and can be used as a promising lead for the development of new antitumor agents.
中文翻译：
含硒的4-苯胺基喹唑啉衍生物作为新型抗有丝分裂剂的合成及生物学评价
设计，合成并评估了28种新型的含硒的4-苯胺基喹唑啉衍生物作为抗增殖剂。它们中的大多数具有显着的体外活性，特别是对于化合物23a，25a和25d而言，它们还显示出对顺铂耐药细胞系和阿霉素耐药细胞系最有效的抗肿瘤活性，对正常细胞的良好选择性以及明显的抑制作用对A549细胞系迁移的影响。进一步的机械研究表明，23a，25a和25d诱导A549细胞G2 / M期停滞和凋亡，这与线粒体膜电位的崩溃，某些细胞周期相关蛋白和凋亡相关蛋白的表达改变以及细胞内ROS水平升高有关。最后，化合物23a，25a和25d在没有明显毒性迹象的情况下，也能有效抑制A549异种移植模型中的肿瘤生长。综上所述，这些体外和体内结果表明23a，25a和25d可能是有希望的微管稳定剂，并且可以用作开发新的抗肿瘤剂的有希望的先导。
更新日期：2018-03-06
中文翻译：
含硒的4-苯胺基喹唑啉衍生物作为新型抗有丝分裂剂的合成及生物学评价
设计，合成并评估了28种新型的含硒的4-苯胺基喹唑啉衍生物作为抗增殖剂。它们中的大多数具有显着的体外活性，特别是对于化合物23a，25a和25d而言，它们还显示出对顺铂耐药细胞系和阿霉素耐药细胞系最有效的抗肿瘤活性，对正常细胞的良好选择性以及明显的抑制作用对A549细胞系迁移的影响。进一步的机械研究表明，23a，25a和25d诱导A549细胞G2 / M期停滞和凋亡，这与线粒体膜电位的崩溃，某些细胞周期相关蛋白和凋亡相关蛋白的表达改变以及细胞内ROS水平升高有关。最后，化合物23a，25a和25d在没有明显毒性迹象的情况下，也能有效抑制A549异种移植模型中的肿瘤生长。综上所述，这些体外和体内结果表明23a，25a和25d可能是有希望的微管稳定剂，并且可以用作开发新的抗肿瘤剂的有希望的先导。
京公网安备 11010802027423号