Dereplication of antimalarial constituents of Artemisia oliveriana Bunge using molecular networking and molecular docking analyses

Abstract

Malaria is a potentially life-threatening illness caused by Plasmodium falciparum. In 2020, 241 million cases of malaria were estimated in 85 countries where the disease is endemic, indicating an increase from 227 million cases in 2019. In recent years, medicinal plants have become a focus of research as a potential source of antimalarial compounds. Artemisia oliveriana Bunge, an Iranian native plant, which is mainly found in the eastern region of Isfahan province, has revealed high potential for treatment of malaria, microbial infections and cancer. An important challenge in natural product discovery is rapid dereplication of known entities from complex biological extracts. Various novel bioinformatics approaches such as molecular networking (MN) have emerged recently and provided new perspective for early metabolite identification in natural products (NPs) research. Here we propose an innovative dereplication strategy based on the combination of MN with an extensive in-silico MS/MS fragmentation database of NPs which led to the rapid identification of nine compounds from the aqueous fraction of methanolic extract of A. oliveriana. Dereplicated compounds were trimethyl glycine, 3,4-dicaffeoylquinic acid, 1-methyl histamine, acetyl proline, 2-hydroxyisovaleric acid, 3-hydroxyisovaleric acid, holostyligone, pyridoxine and hordenine. In addition, a molecular docking analysis was applied to evaluate the antimalarial potential of all 9 compounds thorough inhibition of the activity of dihydroorotate dehydrogenase (DHODH) enzyme, as a target for malaria treatment. Acetyl proline indicated highest affinity to the enzyme with a docking score value of -8.09 kcal/mol. Hydroxychloroquine, which was used as the positive control, showed a docking score of -4.06 kcal/mol, as well.