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 / Emanuele, C., Gabriele, C., Alberto, C., Roberta, B., Pierfranco, I., Raffaella, S., Domenico, S., Barbara, C., Fabio, F., Maria, F., Rosanna, M., Gasparrini, F., Ciogli, A., Philip J., S., Frank J., D.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 49:17(2006), pp. 5206-5216. [10.1021/jm0604373]
Calcium channel antagonists discovered by a multidisciplinary approach
GASPARRINI, Francesco;CIOGLI, Alessia;
2006
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
