College of Chemical Engineering, Nanjing Forestry University, Nanjing, China.
Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing, China.
Chem Biol Drug Des. 2019 Aug;94(2):1457-1466. doi: 10.1111/cbdd.13522. Epub 2019 Apr 29.
A series of novel isolongifoleno[7,8-d]thiazolo[3,2-a]pyrimidine derivatives (4a-4x) were synthesized from isolongifolanone according fragment-based design strategy, and their anticancer activity against human aortic smooth muscle cells (HASMC), human breast cancer (MCF-7) cells, human cervical cancer (HeLa) cells, and human liver cancer (HepG2) cells were investigated. Results of the anticancer activity illustrated that most of the compounds showed potent antitumor activity and compound 4i proved to be the most active derivative with IC values of 0.33 ± 0.24 (for MCF-7 cells), 0.52 ± 0.13 (for HeLa cells), and 3.09 ± 0.11 μM (for HepG2 cells), respectively. Moreover, we assessed the effects of 4i on cell apoptosis, cell cycle distribution, mitochondrial membrane potential, and reactive oxygen species (ROS) generation. The results indicated that compound 4i altered mitochondrial membrane potential and produced ROS leading to cell apoptosis of MCF-7 cells in a dose-dependent manner, however, without affecting cell cycle progression. These findings suggested that 4i was an effective compound and provided a promising candidate for anticancer drugs.
一系列新型异长叶烯并[7,8-d]噻唑并[3,2-a]嘧啶衍生物（4a-4x）是根据片段设计策略，从异长叶酮合成的，并对其进行了抗人主动脉平滑肌细胞（HASMC）、人乳腺癌（MCF-7）细胞、人宫颈癌（HeLa）细胞和人肝癌（HepG2）细胞的抗癌活性进行了研究。抗癌活性结果表明，大多数化合物表现出很强的抗肿瘤活性，化合物 4i 被证明是最有效的衍生物，其 IC 值分别为 0.33±0.24（用于 MCF-7 细胞）、0.52±0.13（用于 HeLa 细胞）和 3.09±0.11μM（用于 HepG2 细胞）。此外，我们评估了 4i 对细胞凋亡、细胞周期分布、线粒体膜电位和活性氧（ROS）生成的影响。结果表明，化合物 4i 改变了线粒体膜电位并产生 ROS，导致 MCF-7 细胞凋亡呈剂量依赖性，但不影响细胞周期进程。这些发现表明 4i 是一种有效的化合物，为抗癌药物提供了有希望的候选物。
