Anti-malarial evaluation of some bioactive plant compounds: An integrated computational approach combining QSAR and...

Malaria remains a major global health burden and motivates the search for new antiplasmodial chemotypes. Here, an integrated in-silico workflow was applied to assess four plant-derived compounds such as artemisinin (Artemisia annua L.), chamazulene (Artemisia afra Jacq. ex Willd.), thymol and carvacrol (Thymus vulgaris L.) using molecular docking, QSAR modeling, ADMET prediction, and density functional theory (DFT) calculations. Docking against selected Plasmodium falciparum targets suggested favorable binding for the studied compounds, with chamazulene showing the most favorable predicted affinity toward PfNDH2 (ΔG = -7.7 kcal/mol) and pose-based hydrophobic/π-π contacts. Artemisinin displayed favorable predicted binding to PfPlasmepsin II (ΔG = -7.4 kcal/mol), while thymol and carvacrol showed predicted interactions with Plasmepsin and apicoplast DNA polymerase, respectively. A QSAR model built from 71 antimalarial derivatives using multiple linear regression provided strong predictive performance (R² = 0.940; RMSE = 0.768) within the modeled chemical space. In-silico ADMET assessment indicated overall acceptable drug-likeness trends for the investigated compounds, and acute oral toxicity prediction suggested a high LD₅₀ for artemisinin (4228 mg/kg). DFT descriptors further supported differences in electronic behavior, with carvacrol exhibiting the smallest HOMO-LUMO gap (0.15652 eV), indicative of comparatively higher electronic reactivity. Overall, the combined computational results highlight these natural compounds as candidates for further antimalarial research and provide a framework for prioritizing molecules in future screening efforts.