Department of Pharmacy and Biotechnology, University of Bologna , Via Irnerio 48, 40126, Bologna, Italy.
Department of Chemistry "G. Ciamician", University of Bologna , Via Selmi 2, 40126 Bologna, Italy.
J Med Chem. 2016 Nov 10;59(21):9721-9742. doi: 10.1021/acs.jmedchem.6b00576. Epub 2016 Oct 21.
A novel series of β-lactam derivatives that was designed and synthesized to target RGD-binding and leukocyte integrins is reported. The compound library was evaluated by investigating the effects on integrin-mediated cell adhesion and cell signaling in cell lines expressing αβ, αβ, αβ, αβ, αβ, αβ, and αβ integrins. SAR analysis of the new series of azetidinones enabled the recognition of structural elements associated with integrin selectivity. We obtained selective and potent agonists that could induce cell adhesion and promote cell signaling mediated by αβ, αβ, αβ, or αβ integrin, and antagonists for the integrins αβ and αβ as well as αβ and αβ, preventing the effects elicited by the respective endogenous agonists.
报道了一系列针对 RGD 结合和白细胞整合素的新型β-内酰胺衍生物的设计和合成。通过研究化合物库对表达 αβ、αβ、αβ、αβ、αβ、αβ 和 αβ 整合素的细胞系中整合素介导的细胞黏附和细胞信号转导的影响来评估化合物库。对新型氮杂环丁酮系列的 SAR 分析使人们认识到与整合素选择性相关的结构元件。我们获得了选择性和有效的激动剂，这些激动剂能够诱导由 αβ、αβ、αβ 或 αβ 整合素介导的细胞黏附和促进细胞信号转导，以及针对整合素 αβ 和 αβ 以及 αβ 和 αβ 的拮抗剂，从而阻止各自内源性激动剂引起的作用。
