Synthesis of gallic acid based naphthophenone fatty acid amides as cathepsin D inhibitors.
Synthesis of gallic acid based naphthophenone fatty acid amides as cathepsin D inhibitors.
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DOI：
10.1016/j.bmcl.2006.06.010
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发表时间：
2006-09
影响因子：
2.7
通讯作者：
V. Srivastava;H. Saxena;K. Shanker;J. K. Kumar;Suaib Luqman;M. M. Gupta-M.;S. Khanuja;A. Negi
中科院分区：
文献类型：
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作者：
V. Srivastava;H. Saxena;K. Shanker;J. K. Kumar;Suaib Luqman;M. M. Gupta-M.;S. Khanuja;A. Negi
没食子酸是植物中含量最丰富的酚酸之一，已被修饰成组织蛋白酶D的抑制剂。在已报道的结构与活性关系研究的基础上，提出了该化合物的修饰策略。对合成的萘酮脂肪酸酰胺类化合物进行了体外组织蛋白酶D抑制活性的评价。其中两个化合物显示出显著的抑制活性，其IC50值分别为0.06和0.14μM，而胃抑素是目前已知的最有效的抑制剂(0.0023μM)。研究表明，对基于没食子酸的药效团的这种尝试可能会导致组织蛋白酶D的有效抑制剂。
Gallic acid, one of the most abundant plant phenolic acids, has been modified to cathepsin D protease inhibitors. The strategy of modification was proposed basing on some previously reported structure and activity relationship (SAR) studies. The synthesized naphthophenone fatty acid amide derivatives have been evaluated for in vitro cathepsin D inhibition activity. Two of them have shown significant inhibition activity with IC50values of 0.06 and 0.14μM, respectively, as compared against pepstatin (0.0023μM), the most potent inhibitor known so far. The study revealed that such attempts on gallic acid based pharmacophores might result in potent inhibitors of cathepsin D.