Natural products as starting materials for development of second-generation SERCA inhibitors targeted towards prostate cancer cells

Bioorg Med Chem. 2006 Apr 15;14(8):2810-5. doi: 10.1016/j.bmc.2005.12.001. Epub 2006 Jan 10.


An analysis of the binding of the 8-O-N-tert-butoxycarbonyl-12-aminododecanoyl derivative of 8-O-debutanoylthapsigargin to the target molecule, the SERCA pump, has revealed the importance of the length and flexibility of the side chain attached to O-8. Based on the analysis a series of analogues to the 2-unsubstituted analogue trilobolide has been constructed and shown to be equipotent with thapsigargin as SERCA inhibitors. Only the 12-Boc-aminododecaonoyl derivative, however, was found to be apoptotic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Transporting ATPases / antagonists & inhibitors*
  • Cell Line, Tumor
  • Humans
  • Male
  • Mass Spectrometry
  • Models, Molecular
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / pathology*
  • Rabbits
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases


  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Calcium-Transporting ATPases