Structure-activity relationships of epolactaene derivatives: structural requirements for inhibition of Hsp60 chaperone activity
Structure-activity relationships of epolactaene derivatives: structural requirements for inhibition of Hsp60 chaperone activity
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DOI：
10.1016/j.bmcl.2004.06.054
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发表时间：
2004-09-06
影响因子：
2.7
通讯作者：
Osada, H
中科院分区：
文献类型：
--
作者：
Nagumo, Y;Kakeya, H;Osada, H
Epolactaene是一种从青霉菌中分离得到的代谢产物，它能使人神经母细胞瘤SH-SY 5 Y细胞的细胞周期停滞在G（0）/G（1）期，并诱导神经突的生长。在这篇文章中，我们报告了新的epolactaene衍生物的结构-活性关系（SAR），包括那些缺乏epoxylactam部分和具有各种侧链的衍生物。评价这些衍生物抑制人癌细胞系生长的能力。还分析了它们影响人类热休克蛋白60（Hsp 60）的能力，我们已经确定了Hsp 60是一种与epolactaene结合的蛋白质。我们还确定了epolactaene/ETB（epolactaene叔丁基酯）的重要结构框架，不仅与Hsp 60结合，而且抑制Hsp 60伴侣活性。(C)2004爱思唯尔有限公司保留所有权利。
Epolactaene is a microbial metabolite isolated from the fungal strain Penicillium sp. It arrests the cell cycle at the G(0)/G(1), phase and induces the outgrowth of neurites in human neuroblastoma SH-SY5Y cells. In this communication, we report the structure-activity relationships (SARs) of new epolactaene derivatives, including those lacking the epoxylactam moiety and having various side chains. These derivatives were evaluated for their ability to inhibit the growth of human cancer cell lines. They were also analyzed for their ability to affect human heat shock protein 60 (Hsp60), which we have already identified as a protein that binds to epolactaene. We also identified the important structural framework of epolactaene/ETB (epolactaene tertiary butyl ester) for not only binding to Hsp60 but also inhibiting Hsp60 chaperone activity. (C) 2004 Elsevier Ltd. All rights reserved.