PREDICTED BINDING MODE OF ANDROGRAPHOLIDE AND ITS DERIVATIVES BOUND TO PLASMODIUM FALCIPARUM GERANYLGERANYL PYROPHOSPHATE SYNTHASE

  • Andrianopsyah Mas Jaya Putra Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia.
  • Chaidir Chaidir 3Center for Pharmaceutical and Medical Technology, Agency for the Assessment and Application Technology (BPPT), Tangerang Selatan, Indonesia.
  • Muhammad Hanafi Department of Natural Product, LIPI Research Center for Chemistry, Tangerang Selatan, Indonesia.
  • Arry Yanuar Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia.

Abstract

Objective: Andrographolide is a major secondary metabolite in the Indonesian herb sambiloto (Andrographis paniculata). It displays a moderate
antiplasmodial activity against the chloroquine-resistant strain of Plasmodium falciparum. This study aimed to investigate andrographolide inhibition
of geranylgeranyl pyrophosphate synthase (GGPPS) by andrographolide molecular docking.
Methods: A comparative modeling of P. falciparum GGPPS was conducted using one of the Plasmodium vivax GGPPS crystal structures as a template.
The best model from this comparative modeling was then used in a molecular docking to investigate the binding mode of andrographolide in the
P. falciparum GGPPS active site.
Results: In the P. falciparum GGPPS active site, andrographolide is situated with its double rings pointing toward the hydrophobic pocket, while its
lactone group is positioned between first aspartate-rich motif and second aspartate-rich motif of the catalytic pocket.
Conclusions: In the active site, andrographolide is situated with its double rings pointing toward the hydrophobic pocket, while its lactone group is
positioned in the catalytic pocket.

Keywords: Andrographolide, Plasmodium falciparum, Geranylgeranyl pyrophosphate synthase, Comparative modeling, Molecular docking.

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Supplementary Fig. 3: Left: Docking pose of 1 (light blue sticks), 2a (purple sticks), and 2b (yellow sticks), in Plasmodium falciparum
geranylgeranyl pyrophosphate synthase model; aspartates in first aspartate-rich motif and second aspartate-rich motif depicted in
blue wires and labeled; image captured using PyMOL Molecular Graphics System (at http://www.pymol.org/) [12]. Right: Structures of
andrographolide (1), 2a, and 2b
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How to Cite
Putra, A. M. J., Chaidir, C., Hanafi, M., & Yanuar, A. (2017). PREDICTED BINDING MODE OF ANDROGRAPHOLIDE AND ITS DERIVATIVES BOUND TO PLASMODIUM FALCIPARUM GERANYLGERANYL PYROPHOSPHATE SYNTHASE. International Journal of Applied Pharmaceutics, 9, 94-97. https://doi.org/10.22159/ijap.2017.v9s1.54_60
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