Anti-malarial evaluation activity of some bioactive substances: an advanced computational approach leading to novel drug pre-formulation

Abstract

This study aims to evaluate the effectiveness of four plant compounds as potential antimalarials: Artemisinin from Artemisia annua extract, Chamazulene from Artemisia afra extract, and both Thymol and Carvacrol from Thymus vulgaris (Thyme) extract. The study relied on computational simulation techniques, targeting four key parasite proteins: PFNDH2, Plasmepsin, and PF-Plasmepsin_2, as well as Apicoplast DNA polymerase. Molecular docking results showed strong interactions and precisely defined binding sites, particularly between Chamazulene and PF-Plasmepsin_2 (ΔG = -7.7 kcal/mol) and Artemisinin with PF-NDH2 (ΔG = -7.4kcal/mol). In addition, a Quantitative StructureActivity Relationship (QSAR) model was developed using Multiple Linear Regression (MLR) and Support Vector Regression (SVR), based on a dataset comprising 71 derivatives of known antimalarial compounds. The model demonstrated high predictive accuracy (R² > 0.93, and RMSE < 0.82).