Design, synthesis and biological activity of piperlongumine derivatives as selective anticancer agents

  • Eur J Med Chem. 2014 Jul 23:82:545-51. doi: 10.1016/j.ejmech.2014.05.070.
Yuelin Wu  1 ,  Xiao Min  2 ,  Chunlin Zhuang  2 ,  Jin Li  2 ,  Zhiliang Yu  2 ,  Guoqiang Dong  2 ,  Jiangzhong Yao  2 ,  Shengzheng Wang  2 ,  Yang Liu  2 ,  Shanchao Wu  2 ,  Shiping Zhu  2 ,  Chunquan Sheng  2 ,  Yunyang Wei  3 ,  Huojun Zhang  4 ,  Wannian Zhang  5 ,  Zhenyuan Miao  6
Affiliations
  • 1. 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.
  • 2. School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
  • 3. School of Chemical Engineering, Nanjing University of Science & Technology, 200 Xiaolingwei, Nanjing 210094, People's Republic of China.
  • 4. Department of Radiation Oncology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, People's Republic of China. Electronic address: [email protected].
  • 5. School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China. Electronic address: [email protected].
  • 6. School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China. Electronic address: [email protected].
PMID: 24937186 DOI: 10.1016/j.ejmech.2014.05.070
Abstract

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.

Keywords
Anticancer agent; Biological activity; Piperlongumine; Selectivity.