期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 123, 期 -, 页码 407-418出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2016.07.042
关键词
Chalcogen; Selenium; Cytotoxicity; Apoptosis; Cell cycle arrest
资金
- Plan de Investigacion de la Universidad de Navarra, PIUNA [2014-26]
- Asociacion de Amigos de la Universidad de Navarra
In this work, 27 novel hybrid derivatives containing diverse substituents with chalcogen atoms (selenium or sulfur) and several active heterocyclic scaffolds have been synthesized. Compounds were tested against two human cancer cells lines (MCF7 and PC-3) and a normal human mammary epithelial cell line (184B5) in order to determine their activity and selectivity against malignant cells. Ten compounds showed GI(50) values below 10 mu M in at least one of the cancer cell lines and six of them exhibited a selectivity index higher than 9. In general, selenium-containing compounds were more active than their corresponding sulfur analogs but we found some thiocyanate derivatives with comparable or higher activity and selectivity. Among the different substituents, the seleno- and thio-cyanate groups showed the most promising results. On the basis of their potent activity and high selectivity index, compounds 7e and 8f (containing a thiocyanate and a selenocyanate group, respectively) were selected for further biological evaluation. Both the compounds induced caspase-dependent cell death and cell cycle arrest in G(2)/M phase. In addition, these compounds do not violate any of the Lipinski's Rule of Five and thus possess good potential to become drugs, compound 7e being particularly promising. (C) 2016 Elsevier Masson SAS. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据