Novel tacrine-coumarin hybrids linked to 1,2,3-triazole as anti-Alzheimer’s compounds: In vitro and in vivo biological evaluation and docking study |
| |
| Institution: | 1. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran;2. Department of Medicinal Chemistry, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran;3. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran;4. Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran;5. Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran;6. Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran;7. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran;8. Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran;1. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran;2. Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran;3. Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran;4. Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran;5. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran;1. School of Chemistry, College of Science, University of Tehran, Tehran, Iran;2. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran;3. Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran;4. Department of Medicinal Chemistry, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran;5. Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran;6. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran;1. School of Pharmacy, International Campus (TUMS-IC), Tehran University of Medical Sciences, Tehran, Iran;2. Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran;3. Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran;4. Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran;5. Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran;1. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran;2. Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran;3. Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran;4. Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran;5. Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran;6. Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran;7. Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran;8. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran;9. Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran;1. National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, PR China;2. Department of Pharmacy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi, PR China;3. School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, PR China;4. Pharmaceutical College, Guangxi Medical University, Shuangyong Road, Nanning 530021, Guangxi, PR China;5. Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University, 109 North 2nd Huan Cheng Road, Guilin 541004, PR China |
| |
| Abstract: | A new series of tacrine-coumarin hybrids linked to 1,2,3-triazole were designed, synthesized, and tested as potent dual binding site cholinesterase inhibitors (ChEIs) for the treatment of Alzheimer’s disease (AD). Among them, compound 8e was the most potent anti-AChE derivative (IC50 = 27 nM) and compound 8m displayed the best anti-BChE activity (IC50 = 6 nM) much more active than tacrine and donepezil as the reference drugs. Compound 8e was also evaluated for its BACE1 inhibitory activity and neuroprotectivity against PC12 cells exposed to Aβ25-35 which indicated low activity. Finally, in vivo studies by Morris water maze task showed that compound 8e significantly reversed scopolamine-induced memory deficit in rats. |
| |
| Keywords: | Alzheimer’s disease Tacrine-Coumarins 1 2 3-Triazole Docking study Dual binding site Morris water maze |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
