Author/Authors :
Afshar Davoud نويسنده Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran , Mostoufi Azar نويسنده Research Center of Marine Pharmaceutical Science, Ahvaz Jundishpur University of Medical Science, Ahvaz , Fereidoonnezhad Masood نويسنده Department of Medicinal Chemistry, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. , Aliyan Fariba نويسنده Department of Medicinal Chemistry, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. , Zali Samaneh نويسنده Department of Medicinal Chemistry, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran , Eskandari Maryam نويسنده Department of Medicinal Chemistry, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
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.
