title: Synthesis and evaluation of curcumin-related compounds containing benzyl piperidone for their effects on human cancer cells.
abstract: Eleven curcumin-related compounds containing a benzyl piperidone moiety were synthesized and evaluated for their effects on cultured prostate cancer PC-3 cells, pancreas cancer BxPC-3 cells, colon cancer HT-29 cells and lung cancer H1299 cells. Inhibitory effects of these compounds on the growth of PC-3, BxPC-3, HT-29 and H1299 cells were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and trypan blue exclusion assay. Compounds benzyl piperidone 2 (P2), P4, P7, 4-bromo-2-fluoro-benzyl piperidone 2 (PFBr2), PFBr3 and PFBr4 (see syntheses and structures in Figs. 1, 2) exhibited potent inhibitory effects on the growth of cultured PC-3, BxPC-3, HT-29 and H1299 cells. The IC50 for these compounds was lower than 2 µM in all four cell lines. PFBr4 was 41-, 36-, 40- and 46-fold more active than curcumin for inhibiting the growth of PC-3, BxPC-3, HT-29 and H1299 cells, respectively. The benzyl piperidone-containing compounds studied also stimulated apoptosis in PC-3 cells. Mechanistic studies indicate that the effects of both curcumin and PFBr4 on PC-3 cells were associated with a decrease in phospho-Akt and phospho-extracellular signal-regulated kinase (Erk)1/2. The present study indicates that P2, P4, P7, PFBr2, PFBr3 and PFBr4 may have useful effects on human cancer cells.
authors.affiliation: Allan H Conney Laboratory for Research, Institute of Natural Medicinal Chemistry & Green Chemistry, Guangdong University of Technology.
authors.forename: Dai-Ying
authors.initials: DY
authors.lastname: Zhou
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.forename: Allan H
authors.initials: AH
authors.lastname: Conney
authors.forename: Ning
authors.initials: N
authors.lastname: Ding
authors.forename: Xiao-Xing
authors.initials: XX
authors.lastname: Cui
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Michael
authors.initials: M
authors.lastname: Verano
authors.forename: Su-Qing
authors.initials: SQ
authors.lastname: Zhao
authors.forename: Yan-Xiong
authors.initials: YX
authors.lastname: Fan
authors.forename: Xi
authors.initials: X
authors.lastname: Zheng
authors.forename: Zhi-Yun
authors.initials: ZY
authors.lastname: Du
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003474:Curcumin / Q000031:analogs & derivatives* / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010881:Piperidones / Q000737:chemistry*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D010881:Piperidones; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D003474:Curcumin