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Novel chloroquine loaded curcumin based anionic linear globular dendrimer G2: a metabolomics study on Plasmodium falciparum in vitro using 1H NMR spectroscopy

Published online by Cambridge University Press:  27 February 2020

Taher Elmi
Affiliation:
Department of Parasitology and Mycology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
Mehdi Shafiee Ardestani
Affiliation:
Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
Fateme Hajialiani
Affiliation:
Medical Parasitology Department, School of Medicine-International Campus, Iran University of Medical Sciences, Tehran, Iran
Manijeh Motevalian
Affiliation:
Department of Pharmacology and Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
Maryam Mohamadi
Affiliation:
Biochemistry Department, Pasteur Institute of Iran, Pasteur Avenue, Tehran, Islamic Republic of Iran
Sedigheh Sadeghi
Affiliation:
Biochemistry Department, Pasteur Institute of Iran, Pasteur Avenue, Tehran, Islamic Republic of Iran
Zahra Zamani*
Affiliation:
Biochemistry Department, Pasteur Institute of Iran, Pasteur Avenue, Tehran, Islamic Republic of Iran
Fatemeh Tabatabaie*
Affiliation:
Department of Parasitology and Mycology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
*
Author for correspondence: Fatemeh Tabatabaie, Zahra Zamani, E-mail: tabatabaei.f@iums.ac.ir, Iran.zamani@pasteur.ac.ir
Author for correspondence: Fatemeh Tabatabaie, Zahra Zamani, E-mail: tabatabaei.f@iums.ac.ir, Iran.zamani@pasteur.ac.ir

Abstract

Due to side-effects and inefficiency of the drugs used in malaria treatment, finding alternative medicine with less side-effects has attracted much attention. In this regard, in the present study, nanocomposite synthesized and its effects on the metabolites of P. falciparum were investigated. Subsequent to synthesis of nanocomposites, characterization was carried out using nuclear magnetic resonance (NMR), liquid chromatography-mass spectrometry (LC-MS), scanning electron microscopy, dynamic light scattering and Fourier-transform infrared tests. Solubility and drug release were measured and its toxicity on Vero cell was assessed using the MTT assay. The antiparasitic effect of the nanocomposite on the metabolites of P. falciparum was investigated by 1H NMR spectroscopy. Among synthesized nanocomposites, the average size of 239 nm showed suitable solubility in water as well as slow drug release. The MTT assay showed no toxicity for Vero cell lines. Concentrations of 2.5 μg mL−1 of nanocomposite eliminated 82.6% of the total parasites. The most effected metabolic cycles were glyoxylate and dicarboxylate metabolism. In this study, 1H NMR spectroscopy was used with untargeted metabolomics to study the effect of the nanocomposite on P. falciparum. Playing an essential role in understanding drug-target interactions and characterization of mechanism of action or resistance exhibited by novel antiprotozoal drugs, can be achieved by targeting metabolic using LC-MS.

Type
Research Article
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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