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Molecular docking analysis of enaminocarboxamide-based small molecules against Acetylcholine Esterase, drug-likeness, and ADMET prediction
1 , * 2 , 1
1  Laboratory of Applied Organic Chemistry, Bioorganic Chemistry group, Chemistry Department, Sciences Faculty, Badji-Mokhtar-Annaba University, Box 12, Annaba 23000, Algeria
2  Laboratory of Applied Organic Chemistry, Sciences Faculty, Badji-Mokhtar-Annaba University, Box 12, 23000, Annaba, Algeria
Academic Editor: Maria Emília Sousa (registering DOI)

Finding treatments to neurodegenerative diseases such as Alzheimer’s disease AD is one of the biggest challenges for scientists working in the medicinal field, due to the fact that these pathologies are complex, difficult to prevent, and multifactorial. Indeed, AD progression involves different proteins and enzymes including acetylcholine esterase AChE. There is no cure for AD, but there is symptomatic treatments in which the AChE inhibitors takes the major place, that is what made AChE the main drug target in the conception of new anti-AD agents.

Our interest was sought to a specific class of small molecules containing the enaminocarboxamide scaffold combining both enaminone and primary amide moieties. A docking simulation was performed to explore the binding mode of studied compounds and the active site of AChE (PDB: 1ACJ) using Schrödinger suite for the docking calculation and Chimera for the 3D visualization. The studied derivatives showed a great stability inside the cavity of AChE with a docking score included between -9.685 and -8.726 kcal.mol-1. This stability was supported by different interactions with the key residues of the active site including hydrogen bonds with His440, a water bridge with Trp84 as well as pi-pi stacking with Trp84 and Phe330. Additional interactions were perceived with Ser200 and Tyr121 residues. The promising results of docking simulation prompted us to complete the in silico investigation by predicting drug-likeness and ADME properties of the studied compounds using MolSoft and SwissADME as accurate predictive tools.

Keywords: Enaminocarboxamide; Acetylcholine Esterase; Alzheimer’s disease, Docking simulation.
Comments on this paper
Eduvan Daniel Valencia Cristancho
Excellent work, finding new inhibitors of pharmacological targets mediating a degenerative disease, as in this case Alzheimer's, are crucial for the advancement of different therapies. The obtained values of molecular docking and oral bioavailability are in very promising ranges compared to currently used reference drugs.