Synthesis, pharmacology and molecular docking on multifunctional tacrine-ferulic acid hybrids as cholinesterase inhibitors against Alzheimer's disease.
| 作者： | Zhu Jie, Yang Hongyu, Chen Yao, Lin Hongzhi, Li Qi, Mo Jun, Bian Yaoyao, Pei Yuqiong, Sun Haopeng |
| 作者单位： |
1a Department of Medicinal Chemistry , China Pharmaceutical University , Nanjing , China. 2b School of Pharmacy , Nanjing University of Chinese Medicine , Nanjing , China. 3c School of Nursing , Nanjing University of Chinese Medicine , Nanjing , China. |
| 刊名： | Journal of enzyme inhibition and medicinal chemistry, 2018, Vol.33 (1), pp.496-506 |
| 来源数据库： | PubMed Journal |
| DOI： | 10.1080/14756366.2018.1430691 |
| 关键词： | Alzheimer’s disease; Cholinesterase inhibitor; Molecular docking; Multi-target ligand; Tacrine-ferulic hybrid; |
| 原始语种摘要： | The cholinergic hypothesis has long been a "polar star" in drug discovery for Alzheimer's disease (AD), resulting in many small molecules and biological drug candidates. Most of the drugs marketed for AD are cholinergic. Herein, we report our efforts in the discovery of cholinesterases inhibitors (ChEIs) as multi-target-directed ligands. A series of tacrine-ferulic acid hybrids have been designed and synthesised. All these compounds showed potent acetyl-(AChE) and butyryl cholinesterase(BuChE) inhibition. Among them, the optimal compound 10g, was the most potent inhibitor against AChE (electrophorus electricus (eeAChE) half maximal inhibitory concentration (IC50) = 37.02 nM), it was also a strong inhibitor against BuChE (equine serum (eqBuChE) IC50 = 101.40 nM).... |
