Open AccessANDROGRAPHOLIDE AND ITS DERIVATIVE - A STORY OF ANTIMALARIAL DRUG DESIGN AND SYNTHESIS
Author(s) -
Andrianopsyah Mas Jaya Putra,
. Chaidir,
Muhammad Hanafi,
Yuanjiang Pan,
Arry Yanuar
Publication year - 2017
Publication title -
international journal of applied pharmaceutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.238
H-Index - 15
ISSN - 0975-7058
DOI - 10.22159/ijap.2017.v9s1.55_61
Subject(s) - andrographolide , chemistry , derivative (finance) , plasmodium falciparum , plasmodium vivax , stereochemistry , nuclear magnetic resonance spectroscopy , combinatorial chemistry , malaria , organic chemistry , biology , financial economics , immunology , economics
Objective: Andrographolide was found to show moderate antimalarial activity against chloroquine-resistant strain of Plasmodium falciparum (PF). Itthus becomes an interesting lead for new antimalarial drugs. This study describes a molecular docking of andrographolide and its derivative into thebest 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 modelwas considered suitable for molecular docking. Partition coefficient of andrographolide was determined to assist its derivative design based onhydrophobicity 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 ofandrographolide’s derivative was higher (+1.89), compared to that of andrographolide of +1.62. The NMR data of second and third synthesisexperiments were consistent at the 5-mmol scale.Conclusions: On the molecular docking of andrographolide into the model, an antimalarial andrographolide derivative design that is morehydrophobic than andrographolide was proposed since the stronger hydrophobicity property of drug, the better of its activity of the drug. Synthesisof this derivative with a simple and green procedure was found to be reproducible.