Homology Modelling and Molecular Docking Studies of Selected Substituted Benzo[d ]imidazol-1-yl)methyl)benzimidamide Scaffolds on Plasmodium falciparum Adenylosuccinate Lyase Receptor

Bioinformatics and Biology Insights
Gbolahan O OduseluEzekiel Adebiyi

Abstract

Plasmodium falciparum adenylosuccinate lyase (PfADSL) is an important enzyme in purine metabolism. Although several benzimidazole derivatives have been commercially developed into drugs, the template design as inhibitor against PfADSL has not been fully explored. This study aims to model the 3-dimensional (3D) structure of PfADSL, design and predict in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) of 8 substituted benzo[d]imidazol-1-yl)methyl)benzimidamide compounds as well as predict the potential interaction modes and binding affinities of the designed ligands with the modelled PfADSL. PfADSL 3D structure was modelled using SWISS-MODEL, whereas the compounds were designed using ChemDraw Professional. ADMET predictions were done using OSIRIS Property Explorer and Swiss ADME, whereas molecular docking was done with AutoDock Tools. All designed compounds exhibited good in silico ADMET properties, hence can be considered safe for drug development. Binding energies ranged from -6.85 to -8.75 kcal/mol. Thus, they could be further synthesised and developed into active commercial antimalarial drugs.

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Citations

May 6, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Noor Zafirah IsmailHasni Arsad
Apr 30, 2021·Parasitology International·Nobuaki YasuoMasakazu Sekijima
Aug 28, 2021·Advances and Applications in Bioinformatics and Chemistry : AABC·Mathewos AnzaBelen Abarca

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Software Mentioned

PyMOL
Clustal Omega
LigPlot
SwissADME
FRee
AutoDock4
Computed Atlas of Surface Topography of ( CASTp )
Online druG 3D conformation generator
ChemDraw
OSIRIS Property Explorer

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