Illudalic acid as a potential LAR inhibitor: Synthesis, SAR, and preliminary studies on the mechanism of action
Illudalic acid as a potential LAR inhibitor: Synthesis, SAR, and preliminary studies on the mechanism of action
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DOI：
10.1016/j.bmc.2008.06.014
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发表时间：
2008-08-01
影响因子：
3.5
通讯作者：
Shen, Jingkang
中科院分区：
文献类型：
--
作者：
Ling, Qing;Huang, Yue;Shen, Jingkang
本文报道了人白细胞共同抗原相关（LAR）磷酸酶抑制剂衣草酸的一种新的合成方法。阳离子。合成了一系列更简单的衣草酸类似物，并评价了其抑制LAR的效力。构效关系（SAR）研究表明，5-甲酰基和半缩醛内酯对有效抑制LAR活性至关重要，是衣尔达酸的关键药效团。稠合的二甲基环戊烯环部分明显有助于增强衣草酸对LAR的效力。采用电喷雾质谱（ESI-MS）和分子对接技术对衣草酸抗LAR的作用机制进行了初步研究。结果与所描述的机理完全一致。(C)2008爱思唯尔有限公司保留所有权利。
A novel synthesis of the human leukocyte common antigen-related (LAR) phosphatase inhibitor, illudalic acid, has been achieved by a route more amenable to structure modi. cations. A series of simpler analogues of illudalic acid was synthesized and evaluated for potency in inhibiting LAR. The structure -activity relationship (SAR) study has shown that the 5-formyl group and the hemi-acetal lactone are crucial for effective inhibition of LAR activity, and are the key pharmacophores of illudalic acid. The fused dimethylcyclopentene ring moiety evidently helps to enhance the potency of illudalic acid against LAR. A preliminary study of the mechanism of action of illudalic acid against LAR was conducted using electrospray ionization mass spectrometry (ESI-MS) and molecular docking techniques. The results are in full agreement with the described mechanism. (C) 2008 Elsevier Ltd. All rights reserved.