Molecular modelling approaches can reveal the Molecular interactions established between antimalarial targets of hemozoin pathway and the organic phytochemicals of Artocarpus species.

ABSTRACT

Ayurveda, the traditional Indian medical system, has potential applications in early malaria treatment. In an in silico docking study, 50 phytochemicals from two plants Artocarpus lakoocha Roxb. (AL) And Artocarpus heterophyllus Lam. (AH), were examined for their interactions with anti-malarial proteins (PDB IDs 3BWK, 3BPF, 1LF3). The nucleotide analogue Artemisinin, a current malaria treatment, served as a positive control. Result showed that phytochemicals from AL and AH exhibited binding affinities as high as -9.6 kcal/mol, respectively. Additionally, molecular dynamics simulation for Artocarpin 3BPF demonstrated stable complexes over 100 ns. Notably, Artocarpin and Quercetin displayed higher binding affinities (up to -9.6 as well as -9.5 kcal/mol, respectively) compared to Artemisinin (-7.5 up to kcal/mol), have shown. Pharmacokinetic predictions indicated the compounds were likely non-carcinogenic, water-soluble and biologically safe. In-vitro analysis using ß-Hematin assay supported these findings, suggesting the phytochemicals as Hemozoin pathway inhibitors.