Computational evaluation of Khaya ivorensis against plasmodium falciparum aminopeptidase N (PfM1AP) enzyme: Molecular docking, simulation and ADMET studies

Abstract

The extract obtained from the stem bark of Khaya ivorensis has been utilized for malaria treatment. Given the rising resistance of malaria parasites to current medications, exploring new pharmacological targets is essential. Metalloaminopeptidases, particularly PfM1AP, have been identified as promising targets due to their vital role in the survival of the parasite. This study employed computational modeling to evaluate the binding affinities and interaction characteristics of 165 compounds found in K. ivorensis with PfM1AP. The top five compounds showed binding affinities ranging from −18.306 to −13.073 kcal/mol, significantly higher than the standard ligand's − 7.97 kcal/mol. Among these, pentagalloylglucose displayed the strongest binding affinity and most stable interactions, suggesting its potential as a PfM1AP inhibitor. ADMET analysis revealed some limitations regarding oral bioavailability and permeability through the blood-brain barrier; however, these compounds exhibited favorable safety profiles with low predicted toxicity levels. Despite the pharmacokinetic challenges, their high binding affinities and stable interactions indicate their potential as effective antimalarial agents. These results highlight the need for further experimental validation and optimization to improve the drug-like properties of these compounds, particularly concerning bioavailability and pharmacokinetic issues. Ultimately, this research contributes to the growing body of work aimed at developing innovative antimalarial treatments and lays the groundwork for future studies focused on targeted approaches against malaria.