title: Synthesis and antiproliferative effect of novel curcumin analogues.
abstract: Novel curcumin analogues with α,β-unsaturated ketone moiety and/or α,β-saturated ketone structure were synthesized from curcumin via alkylation at the central carbon and the phenolic hydroxy groups, and hydrogenation of α,β-unsaturated ketone moiety. The antiproliferative activities were tested in five human solid tumor cell lines in vitro. Most of the compounds exhibited increased antiproliferative activities comparing with that of curcumin. Structure-activity relationship (SAR) analysis revealed that the α,β-unsaturated ketone structure was not required for antiproliferative activity of these curcumin analogues. Among these compounds, 1,7-bis(3-methoxy-4-(3-(4-methylpiperazinyl-1-yl)propoxy)phenyl)-4,4-dibenzylheptane-3,5-dione (16f) was the most effective one with IC50 value below 1 µM, which was 9- to 81-fold more potent than curcumin.
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Bingmi
authors.initials: B
authors.lastname: Liu
authors.forename: Mingyu
authors.initials: M
authors.lastname: Xia
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Ji
authors.forename: Liying
authors.initials: L
authors.lastname: Xu
authors.forename: Jinhua
authors.initials: J
authors.lastname: Dong
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: C585890:1,7-bis(3-methoxy-4-(3-(4-methylpiperazinyl-1-yl)propoxy)phenyl)-4,4-dibenzylheptane-3,5-dione; D010879:Piperazines; D003474:Curcumin