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

DOI

10.2991/iccst-15.2015.8How to use a DOI?

Keywords

Antimalarial, andrographolide, plasmepsin, protease inhibitor

Abstract

Malaria parasite encodes several homologues of aspartic proteases such as plasmepsin I, II and IV which are responsible for degradation 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 inhibition constant of Ei = 10.3 kcal/mol; Ki = 0.02 µM (plasmepsin I), Ei = 8.9 kcal/mol; Ki = 0.3 µM (plasmepsin II), Ei = 9.3 kcal/mol; Ki = 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), Ei = 8.8 kcal/mol; Ki = 0.35 µM (plasmepsin IV). According to the result, it was concluded that andrographolide could be developed as protease inhibitor for antimalarial drug.

Copyright

© 2015, the Authors. Published by Atlantis Press.

Open Access

This is an open access article distributed under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).

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TY  - CONF
AU  - Sandra Megantara
AU  - Jutti Levita
AU  - Slamet I. Surantaatmadja
PY  - 2015/01
DA  - 2015/01
TI  - In Silico Study of Andrographolide as Protease Inhibitors for Antimalarial Drug Discovery
BT  - Proceedings of the 3rd International Conference on Computation for Science and Technology
PB  - Atlantis Press
SP  - 36
EP  - 39
SN  - 2352-538X
UR  - https://doi.org/10.2991/iccst-15.2015.8
DO  - 10.2991/iccst-15.2015.8
ID  - Megantara2015/01
ER  -