Abstract：
N-heterocyclic compounds are important molecular scaffolds in the search for new drugs, since most drugs contain heterocyclic moieties in their molecular structure, and some of these classes of heterocycles are able to provide ligands for two or more biological targets. Ketene dithioacetals are important building blocks in organic synthesis and are widely used in the synthesis of N-heterocyclic compounds. In this work, we used double vinylic substitution reactions on ketene dithioacetals to synthesize a small library of heterocyclic derivatives and evaluated their cytotoxic activity in breast and ovarian cancer cells, identifying two benzoxazoles with good potency and selectivity. In silico predictions indicate that the two most active derivatives exhibit physicochemical properties within the range of drug-like compounds and showed potential to interact with HDAC8 and ERK1 cancer-related targets.
摘要：
N-杂环化合物是寻找新药的重要分子支架,由于大多数药物在其分子结构中含有杂环部分，并且这些类型的杂环中的一些能够为两个或更多个生物靶标提供配体。烯酮二硫缩醛是有机合成中的重要组成部分，广泛用于N-杂环化合物的合成。在这项工作中,我们使用双乙烯取代反应对乙烯酮二硫缩醛合成杂环衍生物的小文库，并评估其在乳腺癌和卵巢癌细胞的细胞毒活性，鉴定两种具有良好效力和选择性的苯并恶唑。计算机模拟预测表明，两种最具活性的衍生物在药物样化合物的范围内表现出物理化学性质，并显示出与HDAC8和ERK1癌症相关靶标相互作用的潜力。
