Exploring the Relationship between PheSA Scores and Ligand Efficiency in the Discovery of Potent Antimalarials: A Computational Perspective

Exploring the Relationship between PheSA Scores and Ligand Efficiency in the Discovery of Potent Antimalarials: A Computational Perspective

Pharmacophore Enhanced Shape Alignment (PheSA) compares the similarities of compounds based on their pharmacophoric and geometrical  characteristics. Ligand efficiency is a notion used to maximize the potency and effectiveness of medication candidates by taking into account their molecular weight an...

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Bibliographic Details
Published in:Journal of Tropical Pharmacy and Chemistry (Online) Vol. 8; no. 1
Main Authors: Agede O. Ayodele, Ogunmodede J. Ayodele, Sanni Nasiru, Wasagu I. Musa, Oyedepo Dapo Sunday, Aiyedun Olawale Stephen, Falade C. Olufunke
Format: Journal Article
Language:English
Published: Mulawarman University 01-06-2024
Subjects:
Antimalarial drugs
Cycloguanil Analogues
Ligand Efficiency
PheSA
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Summary:Pharmacophore Enhanced Shape Alignment (PheSA) compares the similarities of compounds based on their pharmacophoric and geometrical  characteristics. Ligand efficiency is a notion used to maximize the potency and effectiveness of medication candidates by taking into account their molecular weight and binding affinity. This study mainly focused on Cycloguanil analogues to evaluate the association between PheSA scores and ligand efficiency in the identification of effective antimalarials. Information on 36 PfDHFR inhibitors, their structures and biological activity was retrieved from the ChEMBL database. Based on shape and pharmacophore similarity, the PheSA algorithm was used to compare the 3D structures of the inhibitors. Based on a de novo synthesis method, 257 new compounds with greater PheSA similarity scores that have a striking resemblance to cycloguanil were created. The PheSA score and ligand efficiency have a moderately positive link (correlation coefficient of 0.675) according to the analysis. However, the virtual screening of cycloguanil analogues based on PheSA similarity scores offers a useful initial evaluation of structural similarity, directing further experimental studies to find interesting substances for the creation of effective antimalarial drug.
ISSN:2087-7099
2407-6090
DOI:10.25026/jtpc.v8i1.609