Hostname: page-component-76d6cb85b7-s74w7 Total loading time: 0 Render date: 2026-07-15T23:31:35.643Z Has data issue: false hasContentIssue false
  • English
  • Français

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 Open the ORCID record for Taher Elmi [Opens in a new window] ,
Mehdi Shafiee Ardestani ,
Fateme Hajialiani ,
Manijeh Motevalian ,
Maryam Mohamadi ,
Sedigheh Sadeghi ,
Zahra Zamani  and
Fatemeh Tabatabaie
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
Get access Rights & Permissions [Opens in a new window]

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.

Keywords

Dendrimer G2malariametabolomicnanocompositeProtozoa

Information

Type
Research Article
Information
Parasitology , Volume 147 , Issue 7 , June 2020 , pp. 747 - 759
Check for updates
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Abbasi, E, Aval, SF, Akbarzadeh, A, Milani, M, Nasrabadi, HT, Joo, SW, Hanifehpour, Y, Nejati-Koshki, K and Pashaei-Asl, R (2014) Dendrimers: synthesis, applications, and properties. Nanoscale Research Letters 9, 247.CrossRefGoogle ScholarPubMed
Akompong, T, Ghori, N and Haldar, K (2000) In vitro activity of riboflavin against the human malaria parasite Plasmodium falciparum. Antimicrobial Agents and Chemotherapy 44, 88–96.CrossRefGoogle ScholarPubMed
Alavidjeh, MS, Haririan, I, Khorramizadeh, MR, Ghane, ZZ, Ardestani, MS and Namazi, H (2010) Anionic linear-globular dendrimers: biocompatible hybrid materials with potential uses in nanomedicine. Journal of Materials Science. Materials in Medicine 21, 1121–1133.CrossRefGoogle ScholarPubMed
Antinori, S, Galimberti, L, Milazzo, L and Corbellino, M (2012) Biology of human malaria plasmodia including Plasmodium knowlesi. Mediterranean Journal of Hematology and Infectious Diseases 4, e2012013–e2012013.CrossRefGoogle ScholarPubMed
Babaei, E, Sadeghizadeh, M, Hassan, ZM, Feizi, MA, Najafi, F and Hashemi, SM (2012) Dendrosomal curcumin significantly suppresses cancer cell proliferation in vitro and in vivo. International Immunopharmacology 12, 226–234.CrossRefGoogle ScholarPubMed
Braga, CBE, Martins, AC, Cayotopa, ADE, Klein, WW, Schlosser, AR, da Silva, AF, de Souza, MN, Andrade, BWB, Filgueira-Júnior, JA, Pinto, WDJ and da Silva-Nunes, M (2015) Side effects of chloroquine and primaquine and symptom reduction in malaria endemic area (Mâncio Lima, Acre, Brazil). Interdisciplinary Perspectives on Infectious Diseases 2015, 346853–346853.CrossRefGoogle Scholar
Bruni, N, Stella, B, Giraudo, L, Della Pepa, C, Gastaldi, D and Dosio, F (2017) Nanostructured delivery systems with improved leishmanicidal activity: a critical review. International Journal of Nanomedicine 12, 5289–5311.CrossRefGoogle ScholarPubMed
Cui, L, Miao, J and Cui, L (2007) Cytotoxic effect of curcumin on malaria parasite Plasmodium falciparum: inhibition of histone acetylation and generation of reactive oxygen species. Antimicrobial Agents and Chemotherapy 51, 488–494.CrossRefGoogle ScholarPubMed
Debnath, S, Salloum, D, Dolai, S, Sun, C, Averick, S, Raja, K and Fata, J (2013) Dendrimer-curcumin conjugate: a water soluble and effective cytotoxic agent against breast cancer cell lines. Anti-Cancer Agents in Medicinal Chemistry 13, 1531–1539.CrossRefGoogle Scholar
Elford, BC, Haynes, JD, Chulay, JD and Wilson, RJ (1985) Selective stage-specific changes in the permeability to small hydrophilic solutes of human erythrocytes infected with Plasmodium falciparum. Molecular and Biochemical Parasitology 16, 43–60.CrossRefGoogle ScholarPubMed
Elmi, T, Gholami, S, Azadbakht, M and Ziaei, H (2014) Effect of chloroformic extract of Tanacetum parthenium in the treatment of Giardia lamblia infection in Balb/c mice. Journal of Mazandaran University of Medical Sciences 23, 157–165.Google Scholar
Elmi, T, Hajialiani, F, Asadi, MR, Orujzadeh, F, Kalantari Hesari, A, Rahimi Esboei, B and Gholami, S (2019) A study on the effect of Zingiber Officinale hydroalcoholic extract on plasmodium berghei in infected mice: an experimental study. Journal of Rafsanjan University of Medical Sciences 18, 353–364.Google Scholar
Erfani-Moghadam, V, Nomani, A, Najafi, F, Yazdani, Y and Sadeghizadeh, M (2014) Design and synthesis of a novel dendrosome and a PEGylated PAMAM dendrimer nanocarrier to improve the anticancer effect of turmeric (Curcuma longa) curcumin. Pathobiology Research 17, 63–77.Google Scholar
Faye, B, Ndiaye, JL, Ndiaye, D, Dieng, Y, Faye, O and Gaye, O (2007) Efficacy and tolerability of four antimalarial combinations in the treatment of uncomplicated Plasmodium falciparum malaria in Senegal. Malaria Journal 6, 80.CrossRefGoogle ScholarPubMed
Ghimire, P, Singh, N, Ortega, L, Rijal, KR, Adhikari, B, Thakur, GD and Marasini, B (2017) Glucose-6-phosphate dehydrogenase deficiency in people living in malaria endemic districts of Nepal. Malaria Journal 16, 214.CrossRefGoogle ScholarPubMed
Ginsburg, H (2010) Malaria parasite stands out. Nature 466, 702–703.CrossRefGoogle ScholarPubMed
Guo, Z (2016) Artemisinin anti-malarial drugs in China. Acta Pharmaceutica Sinica. B 6, 115–124.CrossRefGoogle ScholarPubMed
Han, L, Huang, Q, Nan, P and Zhong, Y (2009) Prediction of potential antimalarial targets of artemisinin based on protein information from whole genome of Plasmodium falciparum. Chinese Science Bulletin 54, 4234.CrossRefGoogle Scholar
Haririan, I, Alavidjeh, MS, Khorramizadeh, MR, Ardestani, MS, Ghane, ZZ and Namazi, H (2010) Anionic linear-globular dendrimer-cis-platinum (II) conjugates promote cytotoxicity in vitro against different cancer cell lines. International Journal of Nanomedicine 5, 63–75.CrossRefGoogle ScholarPubMed
Hung, W-I, Hung, C-B, Chang, Y-H, Dai, J-K, Li, Y, He, H, Chen, S-W, Huang, T-C, Wei, Y, Jia, X-R and Yeh, J-M (2011) Synthesis and electroactive properties of poly(amidoamine) dendrimers with an aniline pentamer shell. Journal of Materials Chemistry 21, 4581–4587.CrossRefGoogle Scholar
Hussain, T, Yogavel, M and Sharma, A (2015) Inhibition of protein synthesis and malaria parasite development by drug targeting of methionyl-tRNA synthetases. Antimicrobial Agents and Chemotherapy 59, 1856–1867.CrossRefGoogle ScholarPubMed
Jafari Iri Sofla, F, Rahbarizadeh, F and Ahmadvand, D (2015) Evaluation of poly(amidoamine) dendrimer surface modification with poly(ethylene glycol) on cytotoxicity reduction. Pathobiology Research 18, 23–38.Google Scholar
Lazaro, JE and Gay, F (1998) Plasmodium falciparum: in vitro cytotoxicity testing using MTT. Journal of Biomolecular Screening 3, 49–53.CrossRefGoogle Scholar
Lo, ST, Kumar, A, Hsieh, JT and Sun, X (2013) Dendrimer nanoscaffolds for potential theranostics of prostate cancer with a focus on radiochemistry. Molecular Pharmaceutics 10, 793–812.CrossRefGoogle ScholarPubMed
Lu, D-Y (2015) 6 – drug combinations. In Lu, D-Y (ed.). Personalized Cancer Chemotherapy. Oxford: Woodhead Publishing, pp. 37–41.CrossRefGoogle Scholar
Makler, MT and Hinrichs, DJ (1993) Measurement of the lactate dehydrogenase activity of Plasmodium falciparum as an assessment of parasitemia. American Journal of Tropical Medicine and Hygiene 48, 205–210.CrossRefGoogle ScholarPubMed
Mehrizi, TZ, Ardestani, MS, Molla Hoseini, MH, Khamesipour, A, Mosaffa, N and Ramezani, A (2018) Novel nano-sized chitosan amphotericin B formulation with considerable improvement against Leishmania major. Nanomedicine (Lond) 13, 3129–3147.CrossRefGoogle ScholarPubMed
Memar, B, Jamili, S, Shahbazzadeh, D and Bagheri, KP (2016) The first report on coagulation and phospholipase A2 activities of Persian gulf lionfish, Pterois russelli, an Iranian venomous fish. Toxicon 113, 25–31.CrossRefGoogle ScholarPubMed
Mukherjee, R, Patra, M, Dutta, D, Banik, M and Basu, T (2016) Tetracycline-loaded calcium phosphate nanoparticle (Tet-CPNP): rejuvenation of an obsolete antibiotic to further action. Biochimica et Biophysica Acta (BBA) – General Subjects 1860, 1929–1941.CrossRefGoogle ScholarPubMed
Namazi, H and Adeli, M (2003) Novel linear-globular thermoreversible hydrogel ABA type copolymers from dendritic citric acid as the A blocks and poly(ethyleneglycol) as the B block. European Polymer Journal 39, 1491–1500.CrossRefGoogle Scholar
Namazi, H and Adeli, M (2005) Dendrimers of citric acid and poly(ethylene glycol) as the new drug-delivery agents. Biomaterials 26, 1175–1183.CrossRefGoogle ScholarPubMed
Namazi, H, Motamedi, S and Namvari, M (2011) Synthesis of new functionalized citric acid-based dendrimers as nanocarrier agents for drug delivery. BioImpacts : BI 1, 63–69.Google ScholarPubMed
Neto, Z, Machado, M, Lindeza, A, do Rosário, V, Gazarini, ML and Lopes, D (2013) Treatment of plasmodium chabaudi parasites with curcumin in combination with antimalarial drugs: drug interactions and implications on the ubiquitin/proteasome system. Journal of Parasitology Research, 2013, 11.CrossRefGoogle ScholarPubMed
Nyamai, DW and Tastan Bishop, Ö (2019) Aminoacyl tRNA synthetases as malarial drug targets: a comparative bioinformatics study. Malaria Journal 18, 34.CrossRefGoogle ScholarPubMed
Olszewski, KL and Llinas, M (2011) Central carbon metabolism of plasmodium parasites. Molecular and Biochemical Parasitology 175, 95–103.CrossRefGoogle ScholarPubMed
Olszewski, KL, Mather, MW, Morrisey, JM, Garcia, BA, Vaidya, AB, Rabinowitz, JD and Llinás, M (2010) Branched tricarboxylic acid metabolism in Plasmodium falciparum. Nature 466, 774.CrossRefGoogle ScholarPubMed
Oyeyemi, O, Morenkeji, O, Afolayan, F, Dauda, K, Busari, Z, Meena, J and Panda, A (2018) Curcumin-artesunate based polymeric nanoparticle; antiplasmodial and toxicological evaluation in murine model. Frontiers in Pharmacology 9, 1–8.Google ScholarPubMed
Pan, B, Cui, D, Xu, P, Huang, T, Li, Q, He, R and Gao, F (2007) Cellular uptake enhancement of polyamidoamine dendrimer modified single walled carbon nanotubes.Google Scholar
Panneerselvam, C, Ponarulselvam, S and Murugan, K (2011) Potential anti-plasmodial activity of synthesized silver nanoparticle using Andrographis paniculata Nees (Acanthaceae). Archives of Applied Science Research 3, 208–2017.Google Scholar
Parvazi, S, Sadeghi, S, Azadi, M, Mohammadi, M, Arjmand, M, Vahabi, F, Sadeghzadeh, S and Zamani, Z (2016) The effect of aqueous extract of cinnamon on the metabolome of Plasmodium falciparum using 1H NMR spectroscopy. Journal of Tropical Medicine 2016, 5.CrossRefGoogle Scholar
Pham, JS, Dawson, KL, Jackson, KE, Lim, EE, Pasaje, CFA, Turner, KEC and Ralph, SA (2013) Aminoacyl-tRNA synthetases as drug targets in eukaryotic parasites. International Journal for Parasitology. Drugs and Drug Resistance 4, 1–13.CrossRefGoogle ScholarPubMed
Rahmani, A, Alsahli, M, Aly, S, Khan, M and Aldebasi, Y (2018) Role of curcumin in disease prevention and treatment. Advanced Biomedical Research 7, 38–38.CrossRefGoogle ScholarPubMed
Reddy, RC, Vatsala, PG, Keshamouni, VG, Padmanaban, G and Rangarajan, PN (2005) Curcumin for malaria therapy. Biochemical and Biophysical Research Communications 326, 472–474.CrossRefGoogle ScholarPubMed
Sahu, A, Kasoju, N and Bora, U (2008) Fluorescence study of the curcumin-casein micelle complexation and its application as a drug nanocarrier to cancer cells. Biomacromolecules 9, 2905–2912.CrossRefGoogle ScholarPubMed
Sonne, M and Jawetz, E (1969) Combined action of carbenicillin and gentamicin on Pseudomonas aeruginosa in vitro. Applied Microbiology 17, 893–896.CrossRefGoogle ScholarPubMed
Tagbor, H, Bruce, J, Browne, E, Randal, A, Greenwood, B and Chandramohan, D (2006) Efficacy, safety, and tolerability of amodiaquine plus sulphadoxine-pyrimethamine used alone or in combination for malaria treatment in pregnancy: a randomised trial. Lancet 368, 1349–1356.CrossRefGoogle ScholarPubMed
Tallarida, RJ (2011) Quantitative methods for assessing drug synergism. Genes & Cancer 2, 1003–1008.CrossRefGoogle ScholarPubMed
Tiwari, B, Pahuja, R, Kumar, P, Rath, SK, Gupta, KC and Goyal, N (2017) Nanotized curcumin and miltefosine, a potential combination for treatment of experimental visceral leishmaniasis. Antimicrobial Agents and Chemotherapy 61, 01169–16.CrossRefGoogle ScholarPubMed
Trager, W and Jensen, JB (1976) Human malaria parasites in continuous culture. Science (New York, N.Y.) 193, 673–675.CrossRefGoogle ScholarPubMed
Turner, J, Graziano, J, Spraggon, G and Schultz, P (2006) Structural plasticity of an aminoacyl-tRNA synthetase active site. Proceedings of the National Academy of Sciences of the USA 103, 6483–6488.CrossRefGoogle ScholarPubMed
Tyagi, P, Singh, M, Kumari, H, Kumari, A and Mukhopadhyay, K (2015) Bactericidal activity of curcumin I is associated with damaging of bacterial membrane. PLoS ONE 10, e0121313.10.1371/journal.pone.0121313CrossRefGoogle ScholarPubMed
Vilmont, M, Azoulay, M and Frappier, F (1990) Metabolism of glutamine in erythrocytes infected with the human malaria parasite: Plasmodium falciparum. Annales de Parasitologie Humaine et Comparee 65, 162–166.CrossRefGoogle ScholarPubMed
Wang, H, Li, Q, Reyes, S, Zhang, J, Zeng, Q, Zhang, P, Xie, L, Lee, PJ, Roncal, N, Melendez, V, Hickman, M and Kozar, MP (2014) Nanoparticle formulations of decoquinate increase antimalarial efficacy against liver stage plasmodium infections in mice. Nanomedicine: Nanotechnology, Biology, and Medicine 10, 57–65.CrossRefGoogle ScholarPubMed
WHO (2019) World malaria report 2019. Licence: CC BY-NC-SA 3.0 IGO, 1–232.Google Scholar
Zia, Q, Mohammad, O, Rauf, MA, Khan, W and Zubair, S (2017) Biomimetically engineered amphotericin B nano-aggregates circumvent toxicity constraints and treat systemic fungal infection in experimental animals. Scientific Reports 7, 11873.CrossRefGoogle ScholarPubMed
Supplementary material: Image

Elmi et al. supplementary material

Figure S3

Download Elmi et al. supplementary material(Image)
Image 285.8 KB
Supplementary material: Image

Elmi et al. supplementary material

Figure S1

Download Elmi et al. supplementary material(Image)
Image 2.3 MB
Supplementary material: Image

Elmi et al. supplementary material

Figure S2

Download Elmi et al. supplementary material(Image)
Image 207.8 KB