A broadly neuroprotective derivative of curcumin
A broadly neuroprotective derivative of curcumin
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DOI：
10.1111/j.1471-4159.2008.05236.x
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发表时间：
2008-05-01
影响因子：
4.7
通讯作者：
Schubert, David
中科院分区：
文献类型：
--
作者：
Liu, Yuanbin;Dargusch, Richard;Schubert, David
植物多酚姜黄素改变神经细胞对某些形式的毒性应激的反应。类固醇类化合物，环己基双酚A，具有广泛的神经保护特性，与姜黄素非常不同。为了将两个生物活性家族整合到单个分子中，合成了姜黄素的吡唑衍生物，称为CNB-001。CNB-001获得了一种新的活性，在神经保护试验中远优于任何一种母体分子的上级，但保留了两者的一些特性。在细胞培养试验中对营养因子戒断、氧化应激、兴奋性毒性和葡萄糖饥饿以及细胞内和细胞外淀粉样蛋白的毒性具有神经保护作用。虽然CNB-001的创建是基于一种不常见的药物设计方法，但它有可能成为治疗涉及神经细胞死亡的多种疾病的主要候选药物。
The plant polyphenolic curcumin alters the response of nerve cells to some forms of toxic stress. The steroid-like compound, cyclohexyl bisphenol A, has broad neuroprotective properties that are very distinct from those of curcumin. To incorporate both families of biological activities into a single molecule, a pyrazole derivative of curcumin, called CNB-001, was synthesized. CNB-001 acquires a new activity and is far superior in neuroprotection assays to either parental molecule, but retains some of the properties of both. It is neuroprotective in cell culture assays for trophic factor withdrawal, oxidative stress, excitotoxicity, and glucose starvation, as well as toxicity from both intracellular and extracellular amyloid. While the creation of CNB-001 was based upon an uncommon approach to drug design, it has the potential of a lead drug candidate for treating multiple conditions involving nerve cell death.