Malaria remains the leading cause of mortality throughout the world. It is caused by an apicomplexan belonging to genus Plasmodium transmitted by Anopheles mosquito. Owing to the development of resistance and decreased sensitivity to the frequently used conventional antimalarial drugs, malaria is still a major challenge for the health sector. From time to time, many new antimalarial drugs have been made but their efficacy is reduced after some time due to development of resistance against them. So, there is a dire need for development of new antimalarial drugs with improved antimalarial efficiency. Herbal medicine has been used by humans since earliest times due to its high efficacy, low side effects and high availability. Compounds extracted from plants belonging to Asteraceae, Apocynaceae, Araliaceae, Apiaceae, Asclepiadaceae, Canellaceae, Guttiferae and Menispermaceae are specially processed to form versatile medicines against a number of diseases. Alantolactone is a sesquiterpene lactone extracted from roots of plants of Asteraceae family and has been widely and successfully used in humans in various drugs due to its antitumor, anti-microbial and anti-inflammatory effects.

In current study, we analyzed the antimalarial effect of alantolactone via in silico molecular docking method. Our investigation revealed that alantolactone strongly interacts with various proteins of Plasmodium including lactate dehydrogenase, falcipain-2, calcium-dependent protein kinase, cGMP-dependent protein kinase and protein kinase 7 that were crucial for its transmission and infection cycle. The binding energies obtained from the binding of alantolactone with the above-mentioned molecules were -8.6kcal/mol, -10.8kcal/mol, -7.9kcal/mol, -9.4kcal/mol and -7.5kcal/mol respectively. Alantolactone interacted with the binding pockets of all of the studied proteins through their residues including ARG109, PRO141, ALA194, ALA194, MET325, GLU321, ARG123, ARG25, VAL30, CYS114, PHE75, VAL186, ARG185, CYS150, LYS153, ILE326, LYS172, LYS172, ALA328, LYS381, LEU702, LYS704 and LYS704. This study revealed that alantolactone can successfully bind with proteins of Plasmodium and affect their functioning. Prediction of toxicity and ADME analysis for drug-like properties suggested that alantolactone is safe to use as an antimalarial drug for humans. To further prove the antimalarial effect of alantolactone, in vivo and in vitro investigations are suggested which may then lead to the use of alantolactone as a potential antimalarial drug with high efficacy against malaria.