Pustaka Ilmiah Universitas Padjadjaran

Abstrak

In Silico Study of Andrographolide as Protease Inhibitors for Antimalarial Drug Discovery

Malaria parasite encodes several homologues of aspartic proteases such as plasmepsin I, II and IV which are responsible for d egradation of host erythrocyte hemoglobin inside the vacuole of parasite food. Hence plasmepsins are novel targets for antimalarial drug discovery. Previous study concluded that Andrographis paniculata herbs extract has been proven to exert antimalarial activity. However, the molecular mechanism of this activity was not described. The objectives of this paper were to investigate the interaction between andrographolide, a major constituent of Andrographis paniculata with the ligand binding domain of plasmepsin I, II and IV, to find the most favorable binding site as well as to predict the binding mode. Pepstatin, a protease inhibitor, was used as standard. Docking studies showed that pepstatin gave better binding interactions to plasmepsin I, II and IV with binding affinity and i nhibition constant of Ei = -10.3 kcal/mol; K i = 0.02 µM (plasmepsin I), Ei = -8.9 kcal/mol; Ki = 0.3 µM (plasmepsin II), Ei = -9.3 kcal/mol; K i = 0.15 µM (plasmepsin IV), respectively, while andrographolide showed Ei = -9.8 kcal/mol; Ki = 0.07 µM (plasmepsin I), Ei = -8.7 kcal/mol; Ki = 0.42 µM (plasmepsin II), E i = -8.8 kcal/mol; K i = 0.35 µM (plasmepsin IV). According to the result, it was concluded that andrographolide could be developed as protease inhibitor for antimalarial drug