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首页> 外文期刊>Journal of Medicinal Chemistry >Structure-activity relationships and molecular modeling analysis of flavonoids binding to the benzodiazepine site of the rat brain GABA(A) receptor complex.
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Structure-activity relationships and molecular modeling analysis of flavonoids binding to the benzodiazepine site of the rat brain GABA(A) receptor complex.

机译：类黄酮与大鼠脑GABA（A）受体复合物的苯并二氮杂位结合的结构-活性关系和分子模型分析。

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摘要

The affinities for the benzodiazepine binding site of the GABA(A) receptor of 21 flavonoids have been studied using [(3)H]flumazenil binding to rat cortical membranes in vitro. We show that flavonoids with high affinity for the benzodiazepine receptor in vitro spanning the whole efficacy range from agonists (1q) to inverse agonists (1l) can be synthesized. The receptor binding properties of the flavonoids studied can successfully be rationalized in terms of a comprehensive pharmacophore model recently developed by Cook and co-workers (Drug Des. Dev. 1995, 12, 193-248), supporting the validity of this model. However, in contrast to the requirement by the model that an interaction with the hydrogen bond-accepting site A2 is necessary for compounds to display inverse agonistic activity, 6-methyl-3'-nitroflavone (1l), which cannot engage in such an interaction, nevertheless displays inverse agonism. The analysis of the binding affinities of 3'- and 4'-substituted flavones in terms of the pharmacophore model has yielded new information for the further development of the pharmacophore model.
机译：使用[（3）H]氟马西尼体外结合大鼠皮质膜研究了21种类黄酮GABA（A）受体的苯二氮卓结合位点的亲和力。我们表明，在体外，从激动剂（1q）到反向激动剂（1l）的整个功效范围，对苯二氮卓受体具有高亲和力的类黄酮可以合成。可以根据库克及其同事最近开发的综合药效团模型（Drug Des。Dev。1995，12，193-248）成功地使所研究的类黄酮的受体结合特性合理化，从而证明了该模型的有效性。但是，与该模型要求与氢键接受位点A2相互作用是化合物显示逆激动活性所必需的相反，6-甲基-3'-硝基黄酮（1l）无法参与这种相互作用，但显示出反向激动。根据药效团模型对3'-和4'-取代的黄酮的结合亲和力进行分析，为药效团模型的进一步发展提供了新的信息。

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