Dipartimento di Scienze Farmaceutiche, Alma Mater Studiorum, Università di Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
Eur J Med Chem. 2012 Feb;48:124-31. doi: 10.1016/j.ejmech.2011.12.003. Epub 2011 Dec 8.
The synthesis and the biological activities of new derivatives 1-3, characterized by the isothiocyanate (ITC) functionalities coming from sulforaphane (SFN), a well-known anticancer natural product, were reported. The most interesting compound of the series was 2. It was chemically characterized by two ITC functionalities mounted on the 1,4,5,8-naphthalentetracarboxylic diimide (NDI) scaffold through two polymethylene chains, each constituted by three carbon units. It demonstrated an IC(50) value in the submicromolar range, more potent than SFN, displaying also the ability to trigger apoptotic induction in the same range by eliciting both extrinsic and intrinsic apoptotic pathways. Finally, it was observed that 2 inhibited the cell growth by blocking the cell cycle in G1 phase.
报告了新衍生物 1-3 的合成及其生物活性，这些衍生物的特点是具有来自萝卜硫素（SFN）的异硫氰酸酯（ITC）官能团，SFN 是一种众所周知的抗癌天然产物。该系列中最有趣的化合物是 2。它通过两条聚亚甲基链，每条由三个碳原子组成，在 1,4,5,8-萘四羧酸二酰亚胺（NDI）支架上化学上被两个 ITC 官能团所修饰。它表现出亚微摩尔范围内的 IC50 值，比 SFN 更有效，还通过引发外在和内在凋亡途径，显示出诱导凋亡诱导的能力。最后，观察到 2 通过阻断细胞周期在 G1 期来抑制细胞生长。
