Marastoni Mauro, Trapella Claudio, Scotti Alessandra, Fantinati Anna, Ferretti Valeria, Marzola Erika, Eleonora Gallerani, Gavioli Riccardo, Preti Delia
a Department of Chemical and Pharmaceutical Sciences , University of Ferrara , Ferrara , Italy.
b Department of Life Sciences and Biotechnology , University of Ferrara , Ferrara , Italy.
J Enzyme Inhib Med Chem. 2017 Dec;32(1):865-877. doi: 10.1080/14756366.2017.1334649.
The ubiquitin-proteasome system has been largely investigated for its key role in protein degradation mechanisms that regulate both apoptosis and cell division. Because of their antitumour activity, different classes of proteasome inhibitors have been identified to date. Some of these compounds are currently employed in the clinical treatment of several types of cancer among which multiple myeloma. Here, we describe the design, chemistry, biological activity and modelling studies of a large series of amino acid derivatives linked to a naphthoquinone pharmacophoric group through variable spacers. Some analogues showed interesting inhibitory potency for the β1 and β5 subunits of the proteasome with IC values in the sub-µm range.
泛素-蛋白酶体系统因其在调节细胞凋亡和细胞分裂的蛋白质降解机制中的关键作用而受到广泛研究。由于其抗肿瘤活性，迄今为止已鉴定出不同类别的蛋白酶体抑制剂。其中一些化合物目前用于多种类型癌症的临床治疗，包括多发性骨髓瘤。在此，我们描述了一系列通过可变间隔基与萘醌药效基团相连的氨基酸衍生物的设计、化学、生物活性和建模研究。一些类似物对蛋白酶体的β1和β5亚基显示出有趣的抑制效力，IC值在亚微摩尔范围内。
