Molecular Docking and PLIF Studies of Novel Tacrine-Naphtoquinone Hybrids Based on Multi-Target-Directed Ligand Approach for Alzheimer’s Disease
| Author | Masood Fereidoonnezhad | en |
| Author | Azar Mostoufi | en |
| Author | Samaneh Zali | en |
| Author | Maryam Eskandari | en |
| Author | Davoud Afshar | en |
| Author | Fariba Aliyan | en |
| Issued Date | 2018-05-31 | en |
| Abstract | Background: Alzheimer’s disease (AD), the most typical type of dementia and memory loss, is a complicated and progressive neurodegenerative disorder. Due to the multi-factorial etiology of AD, the multi-target-directed ligand (MTDL) approach can be a potential method in seeking new drug candidates for this disease. Methods: In this study, over 200 tacrine-naphtoquinone hybrids have been designed and their drug-likeness, molecular docking, and descriptor analysis were conducted to find out a drug candidate with less toxicity and better binding affinity than tacrine. The Docking analysis was conducted using human acetylcholineesterase (1ACJ), human butyrylcholineesterase (4BDS), and β-secretase (BACE1) (1w51) enzymes using Autodock 4.2 and Vina. Results: Promising results were obtained on the types of interactions. Based on molecular docking on 3 targets as well as protein ligand interaction fingerprint (PLIF) studies, the compounds with better results were introduced as good candidates for synthesis. The validity of docking protocols was confirmed using a set of familiar active ligands and decoys on these targets by means of 2 known statistical metrics such as the receiver-operating characteristic (ROC) and Enrichment Factor (EF). Conclusion: Structure activity relationship (SAR) studies, in these class of compounds, show that the hydroxyethylamine, as a linker, is an essential group to improving binding site to AChE and BACE-1 targets. | en |
| DOI | https://doi.org/10.5812/jjnpp.65048 | en |
| Keyword | Multi-Target-Directed Ligand | en |
| Keyword | Drug-Likeness | en |
| Keyword | Molecular Docking | en |
| Keyword | PLIF Studies | en |
| Keyword | Alzheimer’s Disease | en |
| Publisher | Brieflands | en |
| Title | Molecular Docking and PLIF Studies of Novel Tacrine-Naphtoquinone Hybrids Based on Multi-Target-Directed Ligand Approach for Alzheimer’s Disease | en |
| Type | Research Article | en |