Development of Multifunctional Pyrimidinylthiourea Derivatives as Potential Anti-Alzheimer Agents
文献类型：期刊论文
| 作者 | Li, Xiaokang1; Wang, Huan2; Lu, Zhengyu1; Zheng, Xinyu1; Ni, Wei1; Zhu, Jin1; Fu, Yan; Lian, Fulin2,3; Zhang, Naixia3 ; Li, Jian1
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| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2016-09-22 |
| 卷号 | 59期号:18页码:8326-8344 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.6b00636 |
| 文献子类 | Article |
| 英文摘要 | Starting from a screening-hit compound, via structure modifications and optimizations, a series of nonfused and nonassembly pyrimidinylthiourea derivatives (2-5) was designed, synthesized, and evaluated as novel multifunctional agents against Alzheimer's disease. Biological activity results demonstrated that compounds 5r and 5t exhibited potent inhibition and excellent selectivity toward acetylcholinesterase (AChE, Sr, IC50 = 0.204 mu M, SI > 196; St, IC50 = 0.067 mu M, SI > 597), specific metal-chelating ability, significant antioxidant effects, modulation of metal-induced A beta aggregation, inhibition of ROS production by copper redox cycle, low cytotoxicity, and moderate neuroprotection to human neuroblastoma SH-SY5Y cells. Moreover, compound Sr displayed appropriate blood brain barrier (BBB) permeability both in vitro and in vivo and could improve memory and cognitive function of, scopolamine-induced amnesia mice. The multifunctional profiles of Sr and its effectivity in AD mice highlight these structurally distinct pyrimidinylthiourea derivatives as prospective prototypes in the research of innovative multifunctional drugs for Alzheimer's disease. |
| WOS关键词 | MULTITARGET-DIRECTED LIGANDS ; AMYLOID-BETA AGGREGATION ; BLOOD-BRAIN-BARRIER ; CHOLINERGIC HYPOTHESIS ; OXIDATIVE STRESS ; SMALL MOLECULES ; FREE-RADICALS ; DRUG DESIGN ; IN-VIVO ; DISEASE |
| 资助项目 | Fundamental Research Funds for the Central Universities[22A201514054] ; Chinese Postdoctoral Science Foundation[2015M580300] ; National Natural Science Foundation of China[8152200403] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000384035300011 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275885]  |
| 专题 | 药理学第二研究室 |
| 通讯作者 | Li, Jian; Zhang, Haiyan; Mao, Fei |
| 作者单位 | 1.East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, 130 Mei Long Rd, Shanghai 200237, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Xiaokang,Wang, Huan,Lu, Zhengyu,et al. Development of Multifunctional Pyrimidinylthiourea Derivatives as Potential Anti-Alzheimer Agents[J]. JOURNAL OF MEDICINAL CHEMISTRY,2016,59(18):8326-8344. |
| APA | Li, Xiaokang.,Wang, Huan.,Lu, Zhengyu.,Zheng, Xinyu.,Ni, Wei.,...&Mao, Fei.(2016).Development of Multifunctional Pyrimidinylthiourea Derivatives as Potential Anti-Alzheimer Agents.JOURNAL OF MEDICINAL CHEMISTRY,59(18),8326-8344. |
| MLA | Li, Xiaokang,et al."Development of Multifunctional Pyrimidinylthiourea Derivatives as Potential Anti-Alzheimer Agents".JOURNAL OF MEDICINAL CHEMISTRY 59.18(2016):8326-8344. |
入库方式： OAI收割
来源：上海药物研究所
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