Novel dipeptide-like rhodesain inhibitors containing the 3-bromoisoxazoline warhead in a constrained conformation were developed; some of them possess Ki 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.
Development of novel dipeptide-like rhodesain inhibitors containing the 3-bromoisoxazoline warhead in a constrained conformation / Ettari, Roberta; Pinto, Andrea; Previti, Santo; Tamborini, Lucia; Angelo, Ilenia C; LA PIETRA, Valeria; Marinelli, Luciana; Novellino, Ettore; Schirmeister, Tanja; Zappalà, Maria; Grasso, Silvana; De Micheli, Carlo; Conti, Paola. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - 23:21(2015), pp. 7053-7060. [10.1016/j.bmc.2015.09.029]
Development of novel dipeptide-like rhodesain inhibitors containing the 3-bromoisoxazoline warhead in a constrained conformation
LA PIETRA, VALERIA;MARINELLI, LUCIANA;NOVELLINO, ETTORE;
2015
Abstract
Novel dipeptide-like rhodesain inhibitors containing the 3-bromoisoxazoline warhead in a constrained conformation were developed; some of them possess Ki 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
