Department of Chemistry & Biochemistry, Augustana University, 2001 S. Summit Ave., Sioux Falls, SD-57197, USA.
Department of Pediatrics, Section of Neonatal-Perinatal Medicine, University of Oklahoma Health Sciences Center, 1200 Everett Dr., Oklahoma City, OK-73014, USA.
ChemMedChem. 2022 Jul 19;17(14):e202200250. doi: 10.1002/cmdc.202200250. Epub 2022 Jun 9.
Organic isothiocyanates (ITCs) are a class of anticancer agents which naturally result from the enzymatic degradation of glucosinolates produced by Brassica vegetables. Previous studies have demonstrated that the structure of an ITC impacts its potency and mode(s) of anticancer properties, opening the way to preparation and evaluation of synthetic, non-natural ITC analogues. This study describes the preparation of a library of 79 non-natural ITC analogues intended to probe further structure-activity relationships for aryl ITCs and second-generation, functionalized biaryl ITC variants. ITC candidates were subjected to bifurcated evaluation of antiproliferative and antioxidant response element (ARE)-induction capacity against human MCF-7 cells. The results of this study led to the identification of (1) several key structure-activity relationships and (2) lead ITCs demonstrating potent antiproliferative properties.
有机异硫氰酸酯 (ITC) 是一类抗癌剂，它们是由芸薹属蔬菜中产生的硫代葡萄糖苷经酶降解而自然形成的。先前的研究表明，ITC 的结构会影响其效力和抗癌特性的模式，为合成非天然 ITC 类似物的制备和评估开辟了道路。本研究描述了 79 种非天然 ITC 类似物文库的制备，旨在进一步探究芳基 ITC 和第二代、功能化联芳基 ITC 变体的结构-活性关系。将 ITC 候选物进行了分叉评估，以检测其对人 MCF-7 细胞的抗增殖和抗氧化反应元件 (ARE) 诱导能力。本研究的结果确定了 (1) 几个关键的结构-活性关系和 (2) 具有强大抗增殖特性的先导 ITC。
