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.
Calcium channel antagonists discovered by a multidisciplinary approach / Carosati, E., Cruciani, G., Chiarini, A., Budriesi, R., Ioan, P., Spisani, R., Spinelli, D., Cosimelli, B., Fusi, F., Frosini, M., Matucci, R., Gasparrini, F., Ciogli, A., Stephens, P.J., Devlin, F.J.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 49:17(2006), pp. 5206-5216. [10.1021/jm0604373]
Calcium channel antagonists discovered by a multidisciplinary approach
Carosati, Emanuele;
2006-01-01
Abstract
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.Pubblicazioni consigliate
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