In silico pharmacological study of lacourtianal, a new terpenoid isolated from the stem bark of Chrysophyllum lacourtianum De Wild (Sapotaceae) against Alzheimer's disease
Abstract
Urgent need to treat, prevent, delay the onset, slow the progression and reduce the symptoms of Alzheimer's disease (AD) is dictated by the growing number of people affected by the disease. This research requires an in silico approach. The aim of this work was to carry out an in silico pharmacological study of lacourtianal, a new terpenoid against Alzheimer's disease. The structure of lacourtianal and reference drugs were drawn on chemdraw 2D. Energy minimization was performed using the molecular mechanics force field (MM2) and saved in the PDB using chemdraw 3D. The compound's Smiles format was entered into the pk-CSM web servers for ADME/Tox parameter prediction. Conformational site analysis and docking parameters such as binding energy, interaction profiles with AD target residues (AchE, BuchE, β-secretase and GSK-3β) were determined using AutoDock 4.2 and Discovery Studio visualizer. Lacourtianal is a valuable oral drug candidate. It crosses the Blood-brain barrier (BBB) and shows considerable docking scores for AD targets. These scores were higher for BuchE and β-secretase compared with reference compounds. It binds to residues Phe297, Phe 338 and Tyr31, Trp286 in the acyl pocket and peripheral site of AchE, respectively. Importantly, it establishes low-energy interactions (hydrogen and pi) with the His438 residue of the Butyrylcholinesterase catalytic triad. It also establishes favorable interactions with residues Tyr71 and Tyr216, which are residues controlling substrate accessibility to the active site of the BACE1 and GSK 3β enzymes respectively. These results show that lacourtianal has promising therapeutic potential for the treatment of Alzheimer's disease.
Keywords: Lacourtianal, in silico, AchE, BuchE, β-secretase, GSK-3β and AD
Keywords:
Lacourtianal, in silico, AchE, BuchE, β-secretase, GSK-3β, ADDOI
https://doi.org/10.22270/jddt.v13i12.6322References
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