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

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.

Investigation of major amino acid residues of anti-norfloxacin monoclonal antibodies responsible for binding with fluoroquinolones

“…A score close to zero indicates good agreement between the model structure and the target structure of similar size 23 . The obtained GMQE and QMEAN values in this study were in the reliable range 24 .…”

Antioxidant Effects, Antiproliferative Effects, and Molecular Docking of Clinacanthus nutans Leaf Extracts

“…The two major compounds found in the CN-Dcm fraction, palmitic acid and linolenyl alcohol (Figure 3), were subjected to drug-likeness and toxicity prediction using Lipinski's rule of five; this rule determines the consistency of orally active drugs [45]. Lipinski's rule of five [45] states that a drug molecule generally does not violate more than one of the following five rules: molecular mass < 500 Da, high lipophilicity (expressed as LogP < than 5), < 5 hydrogen bond donors, < 10 hydrogen bond acceptors, and molar refractivity between 40 and 130 [46,47]. As displayed in Table 5, linolenyl alcohol and palmitic acid did not violate any rules, suggesting that they could be suitable for oral administration.…”

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