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


Andrianopsyah Mas Jaya Putra, Chaidir Chaidir, Muhammad Hanafi, Arry Yanuar

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.

| PDF |

References


Elyazar IR, Hay SI, Baird JK. Malaria distribution, prevalence,

drug resistance and control in Indonesia. Adv Parasitol 2011;74:

‑75.

Jordão FM, Gabriel HB, Alves JM, Angeli CB, Bifano TD, Breda A,

et al. Cloning and characterization of bifunctional enzyme farnesyl

diphosphate/geranylgeranyl diphosphate synthase from Plasmodium

falciparum. Malar J 2013;12:184.

Artz JD, Wernimont AK, Dunford JE, Schapira M, Dong A,

Zhao Y, et al. Molecular characterization of a novel geranylgeranyl

pyrophosphate synthase from Plasmodium parasites. J Biol Chem

;286(5):3315-22.

Crowther GJ, Napuli AJ, Gilligan JH, Gagaring K, Borboa R,

Francek C, et al. Identification of inhibitors for putative malaria drug

targets among novel antimalarial compounds. Mol Biochem Parasitol

;175(1):21-9.

Pholphana N, Rangkadilok N, Saehun J, Ritruechai S, Satayavivad J.

Changes in the contents of four active diterpenoids at different growth

stages in Andrographis paniculata (Burm.f.) Nees (Chuanxinlian).

Chin Med 2013;8(2):1-12.

Mishra K, Dash AP, Dey N. Andrographolide: A novel antimalarial

diterpene lactone compound from Andrographis paniculata

and its interaction with curcumin and artesunate. J Trop Med

;2011:579518.

Srivastava N, Akhila A. Biosynthesis of andrographolide in

Andrographis paniculata. Phytochemistry 2010;71(11-12):1298-304.

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

Int J App Pharm, Special Issue (October)

Putra et al.

Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA,

McWilliam H, et al. Clustal W and Clustal X version 2.0. Bioinformatics

;23:2947-8.

Kuntal BK, Aparoy P, Reddanna P. EasyModeller: A graphical interface

to MODELLER. BMC Res Notes 2010;3:226.

O’Boyle NM, Banck M, James CA, Morley C, Vandermeersch T,

Hutchison GR. Open Babel: An open chemical toolbox. J Cheminform

;3:33.

Ye L, Wang T, Tang L, Liu W, Yang Z, Zhou J, et al. Poor oral

bioavailability of a promising anticancer agent andrographolide is due

to extensive metabolism and efflux by P-glycoprotein. J Pharm Sci

;100(11):5007-17.

DeLano WL. The PyMOL Molecular Graphics System. Palo Alto, CA:

DeLano Scientific; 2008.




About this article

Title

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

Keywords

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

DOI

10.22159/ijap.2017.v9s1.54_60

Date

30-10-2017

Additional Links

Manuscript Submission

Journal

International Journal of Applied Pharmaceutics
Vol. 9, Special Issue (Oct.), 2017 [PTMDS 2017] Page: 94-97

Online ISSN

0975-7058

Statistics

21 Views | 22 Downloads

Authors & Affiliations

Andrianopsyah Mas Jaya Putra
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia.
Indonesia

Chaidir Chaidir
3Center for Pharmaceutical and Medical Technology, Agency for the Assessment and Application Technology (BPPT), Tangerang Selatan, Indonesia.
Indonesia

Muhammad Hanafi
Department of Natural Product, LIPI Research Center for Chemistry, Tangerang Selatan, Indonesia.
Indonesia

Arry Yanuar
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia.
Indonesia


Refbacks

  • There are currently no refbacks.