Binding of ring-substituted indole-3-acetic acids to human serum albumin.
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 (logK(ow)) computed from retention data on a C(18) 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.
Soskić
Milan
M
Department of Chemistry, Faculty of Agriculture, University of Zagreb, Svetosimunska cesta 25, 10000 Zagreb, Croatia. msoskic@agr.hr
Magnus
Volker
V
D000465:Algorithms; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D003627:Data Interpretation, Statistical; D006801:Humans; D007210:Indoleacetic Acids / Q000737:chemistry*; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D012709:Serum Albumin / Q000737:chemistry*
D007210:Indoleacetic Acids; D012709:Serum Albumin; C030737:indoleacetic acid