Synthesis, biological evaluation and molecular modeling of substituted 2-aminobenzimidazoles as novel inhibitors of acetylcholinesterase and butyrylcholinesterase
文献类型：期刊论文
| 作者 | Zhu JM1; Wu CF2; Li XB1; Wu GS3; Xie S1; Hu QN1; Deng ZX1; Zhu MX[*]4; Luo HR[*]2; Hong XC[*]1 |
| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY
 |
| 出版日期 | 2013 |
| 卷号 | 21期号:14页码:4218-4224 |
| 关键词 | Butyrylcholinesterase Acetylcholinesterase Molecular modeling 2-Aminobenzimidazole Alzheimer's disease |
| 通讯作者 | Michael.X.Zhu@uth.tmc.edu ; luohuairong@mail.kib.ac.cn ; xhy78@whu.edu.cn |
| 合作状况 | 其它 |
| 英文摘要 | A series of novel 2-aminobenzimidazole derivatives were synthesized under microwave irradiation. Their biological activities were evaluated on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). A number of the 2-aminobenzimidazole derivatives showed good inhibitory activities to AChE and BuChE. Among them, compounds 9, 12 and 13 were found to be >25-fold more selective for BuChE than AChE. No evidence of cytotoxicity was observed by MTT assay in PC12 cells or HepG2 cells exposed to 100 mu M of the compounds. Molecular modeling studies indicate that the benzimidazole moiety of compounds 9, 12 and 13 forms a face-to-face pi-pi stacking interaction in a 'sandwich' form with the indole ring of Trp82 (4.09 angstrom) in the active gorge, and compounds 12 and 13 form a hydrogen bond with His438 at the catalytic site of BuChE. In addition, compounds 12 and 13 fit well into the hydrophobic pocket formed by Ala328, Trp430 and Tyr332 of BuChE. Our data suggest the 2-aminobenzimidazole drugs as promising new selective inhibitors for AChE and BuChE, potentially useful to treat neurodegenerative diseases. |
| 收录类别 | SCI |
| 资助信息 | This work was supported by the National Science and Technology Major Project of the Ministry of Science and Tech- nology of China (No. 2012ZX10004801-003-011), Key Project of Chinese Ministry of Education (No. 313040), the Specialized Re- search Fund of the Doctoral Program of Higher Education (No. 20110141120017), and the Fundamental Research Funds for the Central Universities (No. 2012306020201), National Mega Project on Major Drug Development (2011ZX09401-302), the Yunnan pro- vincial government (20080A007 and 2012FB181), and the Fund of State Key Laboratory of Phytochemistry and Plant Resources in West China (P2008-ZZ21, T2009-KF05, and P2010-KF10). |
| 语种 | 英语 |
| WOS记录号 | WOS:000320838200028 |
| 公开日期 | 2014-10-17 |
| 源URL | [http://159.226.149.42:8088/handle/152453/8084]  |
| 专题 | 昆明动物研究所_动物模型与人类重大疾病机理重点实验室 |
| 作者单位 | 1.Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, and Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, Chin 2.State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan 650201, China 3.Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China 4.Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA |
| 推荐引用方式 GB/T 7714 | Zhu JM,Wu CF,Li XB,et al. Synthesis, biological evaluation and molecular modeling of substituted 2-aminobenzimidazoles as novel inhibitors of acetylcholinesterase and butyrylcholinesterase[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2013,21(14):4218-4224. |
| APA | Zhu JM.,Wu CF.,Li XB.,Wu GS.,Xie S.,...&Hong XC[*].(2013).Synthesis, biological evaluation and molecular modeling of substituted 2-aminobenzimidazoles as novel inhibitors of acetylcholinesterase and butyrylcholinesterase.BIOORGANIC & MEDICINAL CHEMISTRY,21(14),4218-4224. |
| MLA | Zhu JM,et al."Synthesis, biological evaluation and molecular modeling of substituted 2-aminobenzimidazoles as novel inhibitors of acetylcholinesterase and butyrylcholinesterase".BIOORGANIC & MEDICINAL CHEMISTRY 21.14(2013):4218-4224. |
入库方式： OAI收割
来源：昆明动物研究所
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