title: Development of novel dipeptide-like rhodesain inhibitors containing the 3-bromoisoxazoline warhead in a constrained conformation.
abstract: Novel dipeptide-like rhodesain inhibitors containing the 3-bromoisoxazoline warhead in a constrained conformation were developed; some of them possess K(i) values in the micromolar range. We studied the structure-activity relationship of these derivatives and we performed docking studies, which allowed us to find out the key interactions established by the inhibitors with the target enzyme. Biological results indicate that the nature of the P2 and P3 substituents and their binding to the S2/S3 pockets is strictly interdependent.
authors.affiliation: Dipartimento di Scienze del Farmaco e Prodotti per la Salute, University of Messina, Viale Annunziata, 98168 Messina, Italy. Electronic address: rettari@unime.it.
authors.forename: Roberta
authors.initials: R
authors.lastname: Ettari
authors.affiliation: Dipartimento di Scienze Farmaceutiche, University of Milan, Via Mangiagalli 25, 20133 Milano, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pinto
authors.affiliation: Dipartimento di Scienze del Farmaco e Prodotti per la Salute, University of Messina, Viale Annunziata, 98168 Messina, Italy.
authors.forename: Santo
authors.initials: S
authors.lastname: Previti
authors.affiliation: Dipartimento di Scienze Farmaceutiche, University of Milan, Via Mangiagalli 25, 20133 Milano, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Tamborini
authors.affiliation: Dipartimento di Scienze del Farmaco e Prodotti per la Salute, University of Messina, Viale Annunziata, 98168 Messina, Italy.
authors.forename: Ilenia C
authors.initials: IC
authors.lastname: Angelo
authors.affiliation: Dipartimento di Farmacia, University of Naples, Via Montesano 49, 80131 Napoli, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: La Pietra
authors.affiliation: Dipartimento di Farmacia, University of Naples, Via Montesano 49, 80131 Napoli, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Marinelli
authors.affiliation: Dipartimento di Farmacia, University of Naples, Via Montesano 49, 80131 Napoli, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.affiliation: Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55099 Mainz, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Schirmeister
authors.affiliation: Dipartimento di Scienze del Farmaco e Prodotti per la Salute, University of Messina, Viale Annunziata, 98168 Messina, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Zappalà
authors.affiliation: Dipartimento di Scienze Chimiche, University of Messina, Via F. Stagno D'Alcontres 31, 98166 Messina, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Grasso
authors.affiliation: Dipartimento di Scienze Farmaceutiche, University of Milan, Via Mangiagalli 25, 20133 Milano, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: De Micheli
authors.affiliation: Dipartimento di Scienze Farmaceutiche, University of Milan, Via Mangiagalli 25, 20133 Milano, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Conti
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D057056:Cysteine Proteases / Q000737:chemistry / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004151:Dipeptides / Q000737:chemistry; D015195:Drug Design; D007555:Isoxazoles / Q000737:chemistry*; D051379:Mice; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D014346:Trypanosoma brucei brucei / Q000187:drug effects
chemical_list: D000981:Antiprotozoal Agents; D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D007555:Isoxazoles; D057056:Cysteine Proteases; D003546:Cysteine Endopeptidases; C446033:rhodesain
keywords: 3-Bromo isoxazoline; Dipeptide-like; Inhibitor; Molecular modeling; Rhodesain