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.

Development of novel dipeptide-like rhodesain inhibitors containing the 3-bromoisoxazoline warhead in a constrained conformation / R. Ettari, A. Pinto, S. Previti, L. Tamborini, I..C. Angelo, V. La Pietra, L. Marinelli, E. Novellino, T. Schirmeister, M. Zappalà, S. Grasso, C. De Micheli, P. Conti. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - 23:21(2015 Nov 01), 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

R. Ettari
Primo
;
A. Pinto
Secondo
;
L. Tamborini;C. De Micheli
Penultimo
;
P. Conti
Ultimo
2015

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.
3-Bromo isoxazoline; Dipeptide-like; Inhibitor; Molecular modeling; Rhodesain
Settore CHIM/08 - Chimica Farmaceutica
1-nov-2015
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/500674
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