title: Synthesis and biological evaluation of norcantharidin derivatives as protein phosphatase-1 inhibitors.
abstract: Cantharidin and norcantharidin display anticancer activity against a broad range of tumor cell lines. In this study, we have synthesized a series of norcantharidin derivatives and evaluated their cytotoxic effects on four human tumor cell lines together with the genetically normal human diploid fibroblast line WI-38. One of our compounds (1S,4R)-3-((4-(4-(4-fluorophenyl)piperazin-1-ylsulfonyl) phenyl)carbamoyl)-7-oxa-bicyclo[2.2.1]heptane-2-carboxylic acid (12) exhibited potent cytotoxic effects on the tumor cell lines A-549, HepG2, HeLa, and HCT-8, whereas it was less toxic to WI-38 cells than its parent compound, norcantharidin. In addition, this compound inhibited protein phosphatase-1 activity and microtubule formation in HeLa cells, and it also interacts with calf thymus DNA.
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
authors.forename: Xiao-Wen
authors.initials: XW
authors.lastname: Guan
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, China. Electronic address: chenshw@lzu.edu.cn.
authors.forename: Shi-Wu
authors.initials: SW
authors.lastname: Chen
authors.affiliation: Experimental Center of Medicine, General Hospital of Lanzhou Military Command, Lanzhou 730050, China; Key Laboratory of Stem Cells and Gene Drug of Gansu Province, General Hospital of Lanzhou Military Command, Lanzhou 730050, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Hui
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006574:Heterocyclic Compounds, 2-Ring / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008870:Microtubules / Q000187:drug effects; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: C000601364:3-((4-(4-(4-fluorophenyl)piperazin-1-ylsulfonyl)phenyl)carbamoyl)-7-oxabicyclo(2.2.1)heptane-2-carboxylic acid; D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors; D006574:Heterocyclic Compounds, 2-Ring; D013449:Sulfonamides; C069741:norcantharidin; D004247:DNA; C427203:calf thymus DNA; D054645:Protein Phosphatase 1
keywords: Cytotoxicity; Microtubules; Norcantharidin; Protein phosphatase-1