کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4414567 1307718 2007 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Investigation of structural requirements for inhibitory activity at the rat and housefly picrotoxinin binding sites in ionotropic GABA receptors using DISCOtech and CoMFA
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست شیمی زیست محیطی
پیش نمایش صفحه اول مقاله
Investigation of structural requirements for inhibitory activity at the rat and housefly picrotoxinin binding sites in ionotropic GABA receptors using DISCOtech and CoMFA
چکیده انگلیسی

A number of widely diverse compounds that show inhibitory activities at the picrotoxinin binding sites in housefly and rat GABA receptors were investigated by using the distance comparison technique (DISCOtech) and comparative molecular field analysis (CoMFA) methods to explore the pharmacophore models and the three-dimensional quantitative structure–activity relationships (3D-QSAR) of the compounds. These compounds consist of three diverse types of noncompetitive GABA receptor antagonists, i.e., trioxabicyclooctanes and their derivatives, picrodendrins and related terpenoids, and fipronil and its analogs. For investigation of the structural requirements for inhibitory activity at the picrotoxinin binding site of GABA receptor, DISCOtech pharmacophore models containing one center of hydrophobic ring and two hydrogen bond acceptor atoms for both housefly-head and rat-brain GABA receptors were constructed, respectively. In particular, the interacting areas in housefly receptors appear to be wider than that in rat receptors, the differences between rat and housefly receptor models implicate the selectivity of noncompetitive GABA receptor antagonists. In addition, corresponding CoMFA models with good statistical indices (r2 > 0.9 and q2 > 0.5) were also obtained. These models can be used as guidance for the development of new compounds with high activities and selectivities.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemosphere - Volume 69, Issue 6, October 2007, Pages 864–871
نویسندگان
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