Calcium channel antagonists discovered by a multidisciplinary approach
Calcium channel antagonists discovered by a multidisciplinary approach
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DOI：
10.1021/jm0604373
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发表时间：
2006-08-24
影响因子：
7.3
通讯作者：
Devlin, Frank J.
中科院分区：
文献类型：
--
作者：
Carosati, Emanuele;Cruciani, Gabriele;Devlin, Frank J.
一个多学科项目导致了新型的、结构多样的L型钙内流阻滞剂（CEBs）的发现。最近报道的一种CEB的绝对构型已通过振动圆二色光谱法确定，以明确配体 - 通道相互作用的立体特异性。此后，进行了一次虚拟筛选程序，目的是从一个可购买化合物的数据库中识别CEBs的新型化学型；为了对有生物筛选价值的结构进行优先级排序，在计算机上对340000个分子进行了筛选。结果，20种化合物在体外进行了测试，功能和结合试验显示出几种有希望作为CEBs的命中化合物。
A multidisciplinary project has led to the discovery of novel, structurally diverse, L-type calcium entry blockers (CEBs). The absolute configuration of a recently reported CEB has been determined by vibrational circular dichroism spectroscopy, to assign the stereospecificity of the ligand-channel interaction. Thereafter, a virtual screening procedure was performed with the aim of identifying novel chemotypes for CEBs, starting from a database of purchasable compounds; 340 000 molecules were screened in silico in order to prioritize structures of interest for bioscreening. As a result, 20 compounds were tested in vitro, and functional and binding assays revealed several hits with promising behavior as CEBs.