Abstract: | Malaria is responsible for more deaths around the world than any other parasitic
disease. Due to the emergence of strains that are resistant to the current
chemotherapeutic antimalarial arsenal, the search for new antimalarial drugs remains
urgent though hampered by a lack of knowledge regarding the molecular mechanisms of
artemisinin resistance. Semisynthetic compounds derived from diterpenes from the
medicinal plant Wedelia paludosa were tested in silico against
the Plasmodium falciparum Ca2+-ATPase, PfATP6. This
protein was constructed by comparative modelling using the three-dimensional
structure of a homologous protein, 1IWO, as a scaffold. Compound 21 showed the best
docking scores, indicating a better interaction with PfATP6 than that of
thapsigargin, the natural inhibitor. Inhibition of PfATP6 by diterpene compounds
could promote a change in calcium homeostasis, leading to parasite death. These data
suggest PfATP6 as a potential target for the antimalarial
ent-kaurane diterpenes. |