Testero Sebastian A, Lee Mijoon, Staran Rachel T, Espahbodi Mana, Llarrull Leticia I, Toth Marta, Mobashery Shahriar, Chang Mayland
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.
ACS Med Chem Lett. 2010 Dec 13;2(2):177-81. doi: 10.1021/ml100254e. eCollection 2011 Feb 10.
Matrix metalloproteinases (MMPs) are important zinc-dependent endopeptidases. Two members of this family of enzymes called gelatinases (MMP-2 and MMP-9) have been implicated in a number of human diseases, including cancer, neurological and cardiovascular diseases, and inflammation, to name a few. We describe in this report the preparation and evaluation of two structural types of thiirane inhibitors that show selectivity toward gelatinases. The biphenyl series targets both gelatinases, whereas the monophenyl analogues exhibit potent inhibition of only MMP-2. The latter structural type also exhibits improved water solubility and metabolic stability, both traits desirable for progress of these molecules forward in gelatinase-dependent animal models of disease.
基质金属蛋白酶（MMPs）是一类重要的锌依赖性内肽酶。该酶家族中的两个成员，即明胶酶（MMP - 2和MMP - 9），与多种人类疾病有关，如癌症、神经和心血管疾病以及炎症等。在本报告中，我们描述了两种对明胶酶具有选择性的硫杂环丙烷抑制剂的制备和评估。联苯系列对两种明胶酶都有作用，而单苯基类似物仅对MMP - 2有强效抑制作用。后一种结构类型还表现出改善的水溶性和代谢稳定性，这两个特性对于这些分子在依赖明胶酶的疾病动物模型中的进一步研究是有利的。
