Zhang Youjun, Ma Hao, Wu Yuelin, Wu Zhongli, Yao Zhengguang, Zhang Wannian, Zhuang Chunlin, Miao Zhenyuan
Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China; Ningxia Medical University, Yinchuan 750004, China.
Bioorg Med Chem Lett. 2017 Jun 1;27(11):2308-2312. doi: 10.1016/j.bmcl.2017.04.035. Epub 2017 Apr 13.
Piperlongumine (PL) is a natural alkaloid with broad biological activities. Twelve analogues have been designed and synthesized with non-substituted benzyl rings or heterocycles in this work. Most of the compounds showed better anticancer activities than the parent PL without apparent toxicity in normal cells. Elevation of cellular ROS levels was one of the main anticancer mechanisms of these compounds. Cell apoptosis and cell cycle arrest for the best compound ZM90 were evaluated and similar mechanism of action with PL was demonstrated. The SAR was also characterized, providing worthy directions for further optimization of PL compounds.
胡椒碱（PL）是一种具有广泛生物活性的天然生物碱。在本研究中，设计并合成了12种具有未取代苄基环或杂环的类似物。大多数化合物显示出比母体PL更好的抗癌活性，且在正常细胞中无明显毒性。细胞内活性氧水平升高是这些化合物的主要抗癌机制之一。对最佳化合物ZM90的细胞凋亡和细胞周期阻滞进行了评估，并证明其与PL具有相似的作用机制。还对构效关系进行了表征，为进一步优化PL化合物提供了有价值的指导。
