Natural products as starting materials for development of second-generation SERCA inhibitors targeted towards prostate cancer cells
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- 作者：Helmer Sø ; hoel ; Anne-Marie Lund Jensen ; Jesper V. Mø ; ller ; Poul Nissen ; Samuel R. Denmeade ; John T. Isaacs ; Carl Erik Olsen and S. Brø ; gger Christensen
- 关键词：SERCA inhibitors ; X-ray structure ; Synthesis ; Thapsigargin
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2006
- 出版时间：15 April 2006
- 年：2006
- 卷：14
- 期：8
- 页码：2810-2815
- 全文大小：256 K
文摘
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.