Nura Suleiman Gwaram
Umaru Musa Yar’adua University, Nigeria
Title: Molecular docking and characterization study of some morpholine derivatives on Acetylcholinesterase Inhibition
Biography
Biography: Nura Suleiman Gwaram
Abstract
Acetylcholinesterase inhibitors with antioxidant activities are considered potential treatments for Alzheimer’s disease (AD). Laboratory findings have shown that oxidative stress may play an important role to the pathogenesis of AD. Mainly from in vitro studies, phenolic componds have been reported to have antioxidant. Therefore, the risk of AD disease might be decreased by intake of antioxidants that neutralize the unfavorable effects of oxidative stress. A number of morpholine derivatives have been described as analgesics and local anesthetics. Understanding of cholinesterase structure and their inhibition is important for effective drug design and treatment of AD. Condensation reaction between 4-(2-aminoethyl)morpholine and 4-(2-aminopropyl)morpholine with 2,4-dihydroxybenzaldehyde or 2,4-dihydroxyacetophenone yields the corresponding ligands. In the crystal structures, one oxygen atom of hydroxyl group connect the adjacent hydrogen aton of the amine group via O1…H1 interactions to form a six membered ring and morpholine moety adopt a chair transformation. Molecular docking is done by using Autodock 4.2, setting at 160x180x176 Gridbox, centered at 115.955, 105.139, -139.962 with 0.375Å spacing. •Ligand is docked well in the hydrophobic pocket of TRP86, TYR119, GLY120, GLY121, TYR124, SER125, GLY126, ALA127, LEU130, TYR133, GLU202, SER203, TYR337, PHE338, HIS447 and GLY448. There are 3 intermolecular hydrogen bonds between: (1)TYR124:OH - LIGAND:O18 (distance: 2.91336 Å) (2) LIGAND:H19 - TYR124:OH (distance: 2.05211 Å) (3) LIGAND:H20 - GLN71:OE1 (distance: 1.92168 Å). In silico molecular modelling revealed that the compounds may positioned themselves in the enzyme’s active-site gorge, interacting with residues in the peripheral anionic subsite (PAS) and acyl binding pocket (ABP).