Naphthoquinones isolated from Eleutherine plicata herb: in vitro antimalarial activity and molecular modeling to investigate their binding modes

CAPES; CNPqUniversidade Federal do Pará. Instituto Ciências da Saúde. Programa de Pós-Graduação em Inovação Farmacêutica. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Tecnologia. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Universidade Federal do Pará. Instituto Ciências da Saúde. Programa de Pós-Graduação em Inovação Farmacêutica. Belém, PA, Brazil / Universidade Federal do Pará. Instituto de Tecnologia. Belém, PA, Brazil.Universidade Federal do Pará. Instituto Ciências da Saúde. Programa de Pós-Graduação em Inovação Farmacêutica. Belém, PA, Brazil.Plasmodium falciparum is the cause of malaria and has become resistant to the drugs used to treat the disease. Therefore, the development for novel compounds with antimalarial activity has become urgent. Plant species, such as naphthoquinone-rich Eleutherine plicata, may provide novel substances that exhibit antimalarial activity and serve as an alternative for the treatment of this disease. From this plant species, ethanol extracts were obtained, fractionated, and the isolated substances eleutherin, and isoleutherin were characterized by nuclear magnetic resonance. There in vitro activity against Plasmodium falciparum was examined using the traditional Microtest method using the extract, fractions, and isolated molecules. Eleutherin and isoleutherin showed the best activity toward the parasite with IC50 values of 10.45 and 8.70 µg/mL, respectively. Characterization of the binding mode of the compounds with a target enzyme and identification of the molecular interactions were revealed via molecular docking results. Eleutherin and isoeleutherin interacted with highly conserved residues from the binding cavity of the cytochrome bc1 complex, a protein found in mitochondria. Therefore, the eleutherin and isoeleutherin naphthoquinones showed antiplasmodial activity with a similar mechanism to that of atovaquone were able to interact with the cytochrome bc1 complex, and showed promise for antimalarial treatments