title: Design, synthesis and biological activity of piperlongumine derivatives as selective anticancer agents.
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.
authors.affiliation: 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.
authors.forename: Yuelin
authors.initials: Y
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Min
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Zhuang
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Yu
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Dong
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Jiangzhong
authors.initials: J
authors.lastname: Yao
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Shengzheng
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Shanchao
authors.initials: S
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Shiping
authors.initials: S
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Chunquan
authors.initials: C
authors.lastname: Sheng
authors.affiliation: School of Chemical Engineering, Nanjing University of Science & Technology, 200 Xiaolingwei, Nanjing 210094, People's Republic of China.
authors.forename: Yunyang
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Radiation Oncology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, People's Republic of China. Electronic address: chyyzhj@hotmail.com.
authors.forename: Huojun
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China. Electronic address: zhangwnk@hotmail.com.
authors.forename: Wannian
authors.initials: W
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China. Electronic address: miaozhenyuan@hotmail.com.
authors.forename: Zhenyuan
authors.initials: Z
authors.lastname: Miao
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004148:Dioxolanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D015394:Molecular Structure; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship; D010881:Piperidones
chemical_list: D000970:Antineoplastic Agents; D004148:Dioxolanes; D017382:Reactive Oxygen Species; C498077:piperlongumine; D010881:Piperidones
keywords: Anticancer agent; Biological activity; Piperlongumine; Selectivity