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 / E.CAROSATI; G.CRUCIANI; A.CHIARINI; R.BUDRIESI; P.IOAN; R.SPISANI; D.SPINELLI; B.COSIMELLI; F.FUSI; M.FROSINI; R. MATUCCI; F.GASPARRINI; A. CIOGLI; P.J. STEPHENS; F.J. DEVLIN. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 49:(2006), pp. 5206-5216.
Calcium channel antagonists discovered by a multidisciplinary approach.
MATUCCI, ROSANNA;
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.File | Dimensione | Formato | |
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