کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1362847 | 981497 | 2007 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Binding of ring-substituted indole-3-acetic acids to human serum albumin Binding of ring-substituted indole-3-acetic acids to human serum albumin](/preview/png/1362847.png)
The plant hormone, indole-3-acetic acid (IAA), and its ring-substituted derivatives have recently attracted attention as promising pro-drugs in cancer therapy. Here we present relative binding constants to human serum albumin for IAA and 34 of its derivatives, as obtained using the immobilized protein bound to a support suitable for high-performance liquid chromatography. We also report their octanol-water partition coefficients (log Kow) computed from retention data on a C18 coated silica gel column. A four-parameter QSPR (quantitative structure–property relationships) model, based on physico-chemical properties, is put forward, which accounts for more than 96% of the variations in the binding affinities of these compounds. The model confirms the importance of lipophilicity as a global parameter governing interaction with serum albumin, but also assigns significant roles to parameters specifically related to the molecular topology of ring-substituted IAAs. Bulky substituents at ring-position 6 increase affinity, those at position 2 obstruct binding, while no steric effects were noted at other ring-positions. Electron-withdrawing substituents at position 5 enhance binding, but have no obvious effect at other ring positions.
A quantitative model is proposed which accurately predicts the binding affinities of ring-substituted indole-3-acetic acids to human serum albumin.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry - Volume 15, Issue 13, 1 July 2007, Pages 4595–4600