title: Novel 3,4-seco bile acid diamides as selective anticancer proliferation and migration agents.
abstract: A series of new seco-A ring bile acid diamides were synthesized, and their antiproliferative activities against PC3M (prostate), HT29 (colon) and ES-2 (ovarian) cancer cell lines were investigated using SRB assays. Most synthesized compounds presented improved antiproliferative activities compared to the parent bile acids (IC50 > 80 μM), especially the piperazine conjugated compound 27 with IC50 values of 1.07, 4.58 and 3.86 μM against PC3M, HT29 and ES-2 cancer cell lines, respectively. In addition, all the tested compounds showed less cytotoxic activity on a noncancerous cell line (HAF), and the most active compound 27 exhibited the highest selectivity (Selectivity Index, SI(PC3M) = 26.3). Furthermore, 27 could also enhance G1 arrest in PC3M cell, revealed by cell cycle analysis, and increase anti-migration activity on PC3M cells, confirmed by transwell migration assay.
authors.affiliation: Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, SCME, East China Normal University, Shanghai 200062, China.
authors.forename: Shi-Wei
authors.initials: SW
authors.lastname: Mao
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Huang
authors.initials: H
authors.lastname: Chen
authors.affiliation: Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, SCME, East China Normal University, Shanghai 200062, China.
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Yu
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Lv
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Ya-Jing
authors.initials: YJ
authors.lastname: Xing
authors.affiliation: Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, SCME, East China Normal University, Shanghai 200062, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Xie
authors.affiliation: Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, SCME, East China Normal University, Shanghai 200062, China; Shanghai Key Laboratory of Green Chemistry and Chemical Processes, SCME, East China Normal University, Shanghai 200062, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China. Electronic address: zfyi@bio.ecnu.edu.cn.
authors.forename: Zhengfang
authors.initials: Z
authors.lastname: Yi
authors.affiliation: Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, SCME, East China Normal University, Shanghai 200062, China. Electronic address: fyang@chem.ecnu.edu.cn.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001647:Bile Acids and Salts / Q000737:chemistry* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003958:Diamide / Q000737:chemistry*; D006801:Humans; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001647:Bile Acids and Salts; D003958:Diamide
keywords: Anticancer; Antiproliferative activity; Cell cycle arrest; Migration; Seco A-ring bile acid diamide; Selectivity