title: Synthesis and anti-metastatic effects of novel chiral ionone alkaloid derivatives.
abstract: Novel chiral ionone alkaloid derivatives were synthesized and evaluated their anti-metastatic effects in human MDA-MB-231 breast cancer cells. The chiral center C-6 of derivatives exerted an important role in response to the anti-metastatic activity. Comparing with a positive control of LY294002, compounds 17b and 19a exhibited potent inhibitory effects on the EGF-induced invasion of MDA-MB-231 cells with IC50 values of 0.026 ± 0.003 and 0.016 ± 0.002 μM, respectively. Moreover, compounds 17b and 19a showed inhibitory effects on the expressions of p-PKCζ and p-integrin β1 in MDA-MB-231 cells in a dose-dependent manner. Thus, compounds 17b and 19a offer potential to be developed as novel anti-metastasis agents.
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, PR China.
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Fang
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, PR China.
authors.forename: Xiao-Ai
authors.initials: XA
authors.lastname: Shou
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, PR China.
authors.forename: Chun-Chun
authors.initials: CC
authors.lastname: Gan
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, PR China; Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, People's Republic of China. Electronic address: duanhq@tmu.edu.cn.
authors.forename: Hong-Quan
authors.initials: HQ
authors.lastname: Duan
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, PR China; Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, People's Republic of China. Electronic address: qinnan@tmu.edu.cn.
authors.forename: Nan
authors.initials: N
authors.lastname: Qin
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000473:pathology; D045792:Norisoprenoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D045792:Norisoprenoids
keywords: Anti-metastatic effect; Chiral ionone alkaloid derivatives; Intergrin β1; PKCζ; Synthesis