Maccari Rosanna, Ottanà Rosaria, Ciurleo Rosella, Vigorita Maria Gabriella, Rakowitz Dietmar, Steindl Theodora, Langer Thierry
Dipartimento Farmaco-chimico, Facoltà di Farmacia, Università di Messina, Viale SS. Annunziata, 98168 Messina, Italy.
Bioorg Med Chem Lett. 2007 Jul 15;17(14):3886-93. doi: 10.1016/j.bmcl.2007.04.109. Epub 2007 May 6.
A number of 5-arylidene-2,4-thiazolidinediones containing a hydroxy or a carboxymethoxy group in their 5-benzylidene moiety have been synthesised and evaluated as in vitro aldose reductase (ALR2) inhibitors. Most of them exhibited strong inhibitory activity, with IC(50) values in the range between 0.20 and 0.70 microM. Molecular docking simulations into the ALR2 active site highlighted that the phenolic or carboxylic substituents of the 5-benzylidene moiety can favourably interact, in alternative poses, either with amino acid residues lining the lipophilic pocket of the enzyme, such as Leu300, or with the positively charged recognition region of the ALR2 active site.
已经合成了一些在其5-亚苄基部分含有羟基或羧甲氧基的5-亚芳基-2,4-噻唑烷二酮，并作为体外醛糖还原酶（ALR2）抑制剂进行了评估。它们中的大多数表现出很强的抑制活性，IC(50)值在0.20至0.70微摩尔之间。对ALR2活性位点进行的分子对接模拟表明，5-亚苄基部分的酚类或羧基取代基可以以不同的构象与酶的亲脂口袋内衬的氨基酸残基（如Leu300）或与ALR2活性位点的带正电荷的识别区域进行有利的相互作用。
