Enhancing artemisinin extraction efficiency with natural solvents and evaluating the antimalarial potential

Malaria remains a major global health burden, with 282 million cases reported in 2024. Although artemisinin-based combination therapies are highly effective, their use is constrained by emerging drug resistance and artemisinin’s poor solubility and bioavailability. The growing global demand for artemisinin and related compounds has driven the search for more sustainable alternatives to traditional extraction methods, which typically rely on hazardous solvents such as hexane, petroleum ether, or halogenated compounds. As alternatives, ionic liquids, biosolvents, and natural deep eutectic solvents have been proposed; however, the chemical diversity of these systems complicates their experimental selection. In this context, the application of computational tools such as the COnductor like Screening MOdel for Realistic Solvents (COSMO-RS) represents a powerful strategy for predicting molecular interactions and guiding the selection of novel and more efficient solvents. In this study, COSMO-RS was initially employed to assess the thermodynamic affinity between different solvents and antimalarial compounds, including artemisinin, quinine, quinidine, tetracycline, artemether, dapsone, and pyrimethamine. The most promising candidates were then used for the extraction of artemisinin from Artemisia annua L., and the extracts were directly evaluated for antimalarial activity against Plasmodium falciparum during the erythrocytic stage. Results indicate that the use of terpenes as solvents leads to enhanced extraction efficiency compared to conventional solvents such as dichloromethane. Moreover, the extracts obtained displayed IC₅₀ values comparable to those of standard artemisinin, reinforcing the potential of these natural solvents as sustainable alternatives for both green extraction processes and for the development of novel antimalarial formulations.