Wu Yuelin, Min Xiao, Zhuang Chunlin, Li Jin, Yu Zhiliang, Dong Guoqiang, Yao Jiangzhong, Wang Shengzheng, Liu Yang, Wu Shanchao, Zhu Shiping, Sheng Chunquan, Wei Yunyang, Zhang Huojun, Zhang Wannian, Miao Zhenyuan
School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China; School of Chemical Engineering, Nanjing University of Science & Technology, 200 Xiaolingwei, Nanjing 210094, People's Republic of China.
School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
Eur J Med Chem. 2014 Jul 23;82:545-51. doi: 10.1016/j.ejmech.2014.05.070. Epub 2014 Jun 2.
In an effort to expand the structure-activity relationship of the natural anticancer compound piperlongumine, we have prepared sixteen novel piperlongumine derivatives with halogen or morpholine substituents at C2 and alkyl substituents at C7. Most of 2-halogenated piperlongumines showed potent in vitro activity against four cancer cells and modest selectivity for lung normal cells. The highly active anticancer compound 11h exhibited obvious ROS elevation and excellent in vivo antitumor potency with suppressed tumor growth by 48.58% at the dose of 2 mg/kg. The results indicated that halogen substituents as electrophilic group at C2 played an important role in increasing cytotoxicity.
为了拓展天然抗癌化合物胡椒碱的构效关系，我们制备了16种新型胡椒碱衍生物，这些衍生物在C2位带有卤素或吗啉取代基，在C7位带有烷基取代基。大多数2-卤代胡椒碱对四种癌细胞显示出强大的体外活性，对肺正常细胞具有一定的选择性。高活性抗癌化合物11h表现出明显的活性氧升高，并且在2 mg/kg剂量下具有出色的体内抗肿瘤效力，可使肿瘤生长抑制48.58%。结果表明，C2位作为亲电基团的卤素取代基在增加细胞毒性方面发挥了重要作用。
