N-Acylaminophenothiazines: Neuroprotective agents displaying multifunctional activities for a potential treatment of Alzheimer's disease
N-Acylaminophenothiazines: Neuroprotective agents displaying multifunctional activities for a potential treatment of Alzheimer's disease
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DOI：
10.1016/j.ejmech.2011.03.003
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发表时间：
2011-06-01
影响因子：
6.7
通讯作者：
Isabel Rodriguez-Franco, Maria
中科院分区：
文献类型：
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作者：
Gonzalez-Munoz, Gema C.;Arce, Mariana R.;Isabel Rodriguez-Franco, Maria
我们以前曾报道N-（3-氯-10H-吩噻嗪-10-基）-3-（二甲氨基）丙酰胺（1）作为一种有效的神经保护剂和选择性丁酰胆碱酯酶抑制剂的多功能特性。在本文中，我们开发了一系列的N-酰氨基吩噻嗪从我们的化合物库或新合成。在微和亚微摩尔浓度下，这些化合物选择性地抑制丁酰胆碱酯酶（BuChE），保护神经元免受外源性和线粒体自由基引起的损伤，表现出低毒性，并可渗透到CNS中。此外，N-（3-氯-10H-吩噻嗪-10-基）-2-（吡咯烷-1-基）乙酰胺（11）调节细胞溶质钙浓度，并保护人神经母细胞瘤细胞免受几种毒性，如L型Ca 2+通道激动剂诱导的钙超载，冈田酸和A β肽诱导的tau过度磷酸化。(C)2011年Elsevier Masson SAS。All rights reserved.
We have previously reported the multifunctional profile of N-(3-chloro-10H-phenothiazin-10-yl)-3-(dimethylamino)propanamide (1) as an effective neuroprotectant and selective butyrylcholinesterase inhibitor. In this paper, we have developed a series of N-acylaminophenothiazines obtained from our compound library or newly synthesised. At micro- and sub-micromolar concentrations, these compounds selectively inhibited butyrylcholinesterase (BuChE), protected neurons against damage caused by both exogenous and mitochondrial free radicals, showed low toxicity, and could penetrate into the CNS. In addition, N-(3-chloro-10H-phenothiazin-10-yl)-2-(pyrrolidin-1-yl)acetamide (11) modulated the cytosolic calcium concentration and protected human neuroblastoma cells against several toxics, such as calcium overload induced by an L-type Ca2+-channel agonist, tau-hyperphosphorylation induced by okadaic acid and A beta peptide. (C) 2011 Elsevier Masson SAS. All rights reserved.