title: Calcium channel antagonists discovered by a multidisciplinary approach.
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.
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Perugia, Via Elce di Sotto 10, 06123 Perugia, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Carosati
authors.forename: Gabriele
authors.initials: G
authors.lastname: Cruciani
authors.forename: Alberto
authors.initials: A
authors.lastname: Chiarini
authors.forename: Roberta
authors.initials: R
authors.lastname: Budriesi
authors.forename: Pierfranco
authors.initials: P
authors.lastname: Ioan
authors.forename: Raffaella
authors.initials: R
authors.lastname: Spisani
authors.forename: Domenico
authors.initials: D
authors.lastname: Spinelli
authors.forename: Barbara
authors.initials: B
authors.lastname: Cosimelli
authors.forename: Fabio
authors.initials: F
authors.lastname: Fusi
authors.forename: Maria
authors.initials: M
authors.lastname: Frosini
authors.forename: Rosanna
authors.initials: R
authors.lastname: Matucci
authors.forename: Francesco
authors.initials: F
authors.lastname: Gasparrini
authors.forename: Alessia
authors.initials: A
authors.lastname: Ciogli
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Stephens
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Devlin
mesh_terms: D000818:Animals; D001665:Binding Sites; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D002942:Circular Dichroism; D019992:Databases as Topic; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D008024:Ligands; D015394:Molecular Structure; D009130:Muscle, Smooth / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects; D010069:Oxadiazoles / Q000737:chemistry / Q000494:pharmacology*; D010210:Papillary Muscles / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D008024:Ligands; D010069:Oxadiazoles