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
Dipartimento di Scienze del Farmaco e Prodotti per la Salute, University of Messina, Viale Annunziata, 98168 Messina, Italy.
Dipartimento di Scienze Farmaceutiche, University of Milan, Via Mangiagalli 25, 20133 Milano, Italy.
Bioorg Med Chem. 2015 Nov 1;23(21):7053-60. doi: 10.1016/j.bmc.2015.09.029. Epub 2015 Sep 21.
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.
开发了具有受限构象的含3-溴异恶唑啉弹头的新型二肽样罗得西亚酶抑制剂；其中一些具有微摩尔范围内的K(i)值。我们研究了这些衍生物的构效关系，并进行了对接研究，这使我们能够找出抑制剂与靶酶建立的关键相互作用。生物学结果表明，P2和P3取代基的性质及其与S2/S3口袋的结合是严格相互依赖的。
