2. Academic Validation
  3. Synthesis and biological evaluation of norcantharidin derivatives as protein phosphatase-1 inhibitors

Synthesis and biological evaluation of norcantharidin derivatives as protein phosphatase-1 inhibitors

  • Bioorg Med Chem Lett. 2015 Jan 15;25(2):363-6. doi: 10.1016/j.bmcl.2014.11.032.
Jie Zhao 1,  Xiao-Wen Guan 1,  Shi-Wu Chen 2,  Ling Hui 3
Affiliations

Affiliations

  • 1 School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
  • 2 School of Pharmacy, Lanzhou University, Lanzhou 730000, China. Electronic address: [email protected].
  • 3 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.
PMID: 25466711 DOI: 10.1016/j.bmcl.2014.11.032
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.

Keywords

Cytotoxicity; Microtubules; Norcantharidin; Protein phosphatase-1.

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