Blockade of Multiple Pathways of P. falciparum by Quinoxaline from Curry Fish (S. hermanni) Using an in silico Approach

Abstract

Introduction: The escalating mortality and morbidity rates due to malaria present an unsolved global health problem. Previous in vivo research has revealed the antimalarial effect of S. hermanni. However, the mechanism of quinoxaline inhibition from curry fish against P. falciparum remains unknown, prompting this in silico investigation to identify inhibition pathways. Objectives: This study aims to uncover the inhibitory mechanism pathways of quinoxaline from S. hermanni against numerous proteins in P. falciparum using an in silico approach. Materials and Methods: The PDB, UniProt, and PubChem databases were utilized to obtain target protein and ligand structures. The Molegro molecular docking tool was employed to assess the interactions between the target protein and ligand and evaluate the protein target and ligand (control or active compound). 3D visualization of the target protein-ligand interaction was conducted using Discovery Studio. Pharmacokinetic and toxicity prediction analysis of quinoxaline was performed using PkCMS. Results: Quinoxaline can bind to P. falciparum proteins through similar amino acid residues or different pathways compared to the controls via inhibitor, active, substrate, and cofactor sites, exhibiting various binding affinities. Pharmacokinetic assays revealed that quinoxaline possesses good water solubility, intestinal absorption, and the ability to penetrate the BBB/CNS. However, it exhibits poor skin permeability and limited distribution properties. It can interfere with the P450 function and demonstrates excellent excretion properties. Toxicity analysis indicated that quinoxaline has no toxic effects but can induce skin sensitization. Conclusion: Quinoxaline from curry fish can effectively block multiple metabolic pathways of P. falciparum and has no toxic effect. However, it still exhibits moderate pharmacokinetic properties.