ANDROGRAPHOLIDE AND ITS DERIVATIVE - A STORY OF ANTIMALARIAL DRUG DESIGN AND SYNTHESIS


Andrianopsyah Mas Jaya Putra, Chaidir . ., Muhammad Hanafi, Yuanjiang Pan, Arry Yanuar

Abstract


Objective: Andrographolide was found to show moderate antimalarial activity against chloroquine-resistant strain of Plasmodium falciparum (PF). It
thus becomes an interesting lead for new antimalarial drugs. This study describes a molecular docking of andrographolide and its derivative into the
best PF geranylgeranyl pyrophosphate synthase (PFGGPPS) model.
Methods: A comparative modeling of PFGGPPS based on a crystal structure of Plasmodium vivax GGPPS was optimized and conducted. This model
was considered suitable for molecular docking. Partition coefficient of andrographolide was determined to assist its derivative design based on
hydrophobicity property. Synthesis of the antimalarial drug was scaled up to 5 mm and identified by13 C- and 1H-nuclear magnetic resonance (NMR)
spectroscopy.
Results: The optimal comparative modeling of PFGGPPS was conducted on chain B (3PH7 chain B). The calculated coefficient partition of
andrographolide’s derivative was higher (+1.89), compared to that of andrographolide of +1.62. The NMR data of second and third synthesis
experiments were consistent at the 5-mmol scale.
Conclusions: On the molecular docking of andrographolide into the model, an antimalarial andrographolide derivative design that is more
hydrophobic than andrographolide was proposed since the stronger hydrophobicity property of drug, the better of its activity of the drug. Synthesis
of this derivative with a simple and green procedure was found to be reproducible.


Keywords


Plasmodium falciparum, Geranylgeranyl pyrophosphate synthase, Andrographolide, Comparative modeling, Molecular docking, Drug design and synthesis.

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About this article

Title

ANDROGRAPHOLIDE AND ITS DERIVATIVE - A STORY OF ANTIMALARIAL DRUG DESIGN AND SYNTHESIS

Keywords

Plasmodium falciparum, Geranylgeranyl pyrophosphate synthase, Andrographolide, Comparative modeling, Molecular docking, Drug design and synthesis.

DOI

10.22159/ijap.2017.v9s1.55_61

Date

30-10-2017

Additional Links

Manuscript Submission

Journal

International Journal of Applied Pharmaceutics
Vol. 9, Special Issue (Oct.), 2017 [PTMDS 2017] Page: 98-101

Online ISSN

0975-7058

Statistics

11 Views | 17 Downloads

Authors & Affiliations

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

Chaidir . .
3BPPT Center for Pharmaceutical and Medical Technology, Tangerang Selatan, Indonesia.
Indonesia

Muhammad Hanafi
Division of Natural Products-Food- Pharmaceuticals, LIPI Research Center for Chemistry, Tangerang Selatan, Indonesia.
Indonesia

Yuanjiang Pan
Department of Chemistry, Laboratory of Natural and Biochemistry, Zhejiang University, Hangzhou, P.R. China.
Indonesia

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


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