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

被引：75

作者：

Sohoel, H

Jensen, AML

Moller, JV

Nissen, P

Denmeade, SR

Isaacs, JT

Olsen, CE

Christensen, SB

机构：

[1] Danish Univ Pharmaceut Sci, Dept Med Chem, DK-2100 Copenhagen, Denmark

[2] Aarhus Univ, Dept Mol Biol, DK-8000 Aarhus C, Denmark

[3] Aarhus Univ, Dept Biophys & Physiol, DK-8000 Aarhus C, Denmark

[4] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA

[5] Royal Vet & Agr Univ, Dept Nat Sci, DK-1870 Frederiksberg C, Denmark

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2006年 / 14卷 / 08期

关键词：

SERCA inhibitors; X-ray structure; synthesis; thapsigargin;

D O I：

10.1016/j.bmc.2005.12.001

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 oil 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. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：2810 / 2815

页数：6

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[4]

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