Metal-assisted synthesis of unsymmetrical magnolol and honokiol analogs and their biological assessment as GABAA receptor ligands.
Metal-assisted synthesis of unsymmetrical magnolol and honokiol analogs and their biological assessment as GABAA receptor ligands.
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DOI：
10.1016/j.bmcl.2014.10.091
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发表时间：
2015-01-15
影响因子：
2.7
通讯作者：
Mihovilovic, Marko D.
中科院分区：
文献类型：
--
作者：
Rycek, Lukas;Puthenkalam, Roshan;Schnuerch, Michael;Ernst, Margot;Mihovilovic, Marko D.
我们合成了天然产物厚朴酚（1）和和厚朴酚（2）的新衍生物，并评价了它们作为GABAA受体活性调节的变构配体。通过金属辅助的交叉偶联反应，在两个连续的步骤中制备新的衍生物。在低GABA浓度下，通过双电极电压钳电生理学在α1β2γ2受体亚型上测试化合物。我们已经确定了几种化合物增强GABA诱导电流（IGABA）的范围类似于或甚至高于铅结构。在3 μM时，化合物8 g使IGABA增加了443倍，而和厚朴酚和厚朴酚分别为162和338倍。此外，在EC 10 -20处的8 g具有与和诺啡肽相比在α1β2γ2和α1β1γ2亚型之间大得多的分离窗口，从而改善亚型选择性。
We present the synthesis of new derivatives of natural products magnolol (1) and honokiol (2) and their evaluation as allosteric ligands for modulation of GABAA receptor activity. New derivatives were prepared via metal assisted cross-coupling reactions in two consecutive steps. Compounds were tested by means of two-electrode voltage clamp electrophysiology at the α1β2γ2 receptor subtype at low GABA concentrations. We have identified several compounds enhancing GABA induced current (IGABA) in the range similar or even higher than the lead structures. At 3 μM, compound 8g enhanced IGABA by factor of 443, compared to 162 and 338 of honokiol and magnolol, respectively. Furthermore, 8g at EC10–20 features a much bigger window of separation between the α1β2γ2 and the α1β1γ2 subtypes compared to honokiol, and thus improved subtype selectivity.
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影响因子：
1.8
作者：
Chen, Chang-Ming;Liu, Yeuk-Chuen
通讯作者：
Liu, Yeuk-Chuen
影响因子：
6.7
作者：
Jada, Srinivas;Doma, Mahendhar Reddy;Kumar, H. M. Sampath
通讯作者：
Kumar, H. M. Sampath
DOI：
10.2174/1568015054863837
发表时间：
2005-09-01
期刊：
Current Medicinal Chemistry - Central Nervous System Agents
影响因子：
--
作者：
Sieghart, W.;Ernst, M.
通讯作者：
Ernst, M.
厚朴酚是厚朴树皮的主要生物活性成分，通过 GABA/苯二氮卓受体复合物在小鼠体内发挥抗癫痫作用
影响因子：
7.3
作者：
Chen, C. R.;Tan, R.;Huang, Z. L.
通讯作者：
Huang, Z. L.
影响因子：
3.7
作者：
Luescher, Benjamin P.;Baur, Roland;Sigel, Erwin
通讯作者：
Sigel, Erwin