scholarly journals Plasmodium falciparum Thioredoxin Reductase (PfTrxR) and Its Role as a Target for New Antimalarial Discovery

Molecules ◽  
2015 ◽  
Vol 20 (6) ◽  
pp. 11459-11473 ◽  
Author(s):  
Sara McCarty ◽  
Amanda Schellenberger ◽  
Douglas Goodwin ◽  
Ngolui Fuanta ◽  
Babu Tekwani ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Thioredoxin Reductase

Specific Inhibitors of Plasmodium falciparum Thioredoxin Reductase as Potential Antimalarial Agents.

ChemInform ◽  
2006 ◽  
Vol 37 (30) ◽  
Author(s):  
A. D. Adricopulo ◽  
M. B. Akoachere ◽  
R. Krogh ◽  
C. Nickel ◽  
M. J. McLeish ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Thioredoxin Reductase ◽  
Antimalarial Agents ◽  
Specific Inhibitors

A proteomic glimpse into the effect of antimalarial drugs on Plasmodium falciparum proteome towards highlighting possible therapeutic targets

2020 ◽  
Author(s):  
Majid Dousti ◽  
Raúl Manzano-Román ◽  
Sajad Rashidi ◽  
Gholamreza Barzegar ◽  
Niloofar Bavarsad Ahmadpour ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Calcium Binding ◽  
Drug Targets ◽  
Thioredoxin Reductase ◽  
Resistance Mechanisms ◽  
Antimalarial Drugs ◽  
Effective Vaccine ◽  
Apical Membrane Antigen 1 ◽  
Clinic Management ◽  
Altered Proteins

Abstract There is no effective vaccine against malaria; therefore, chemotherapy is to date only choice to fight against this infectious disease. However, there are growing evidences of drug-resistance mechanisms in malaria treatments. Therefore, the identification of new drug targets is an urgent need for the clinic management of the disease. Proteomic approaches offer the chance of determining the effects of antimalarial drugs on the proteome of Plasmodium parasites. Accordingly, we here review the effects of antimalarial drugs on Plasmodium falciparum proteome pointing out the relevance of several proteins as possible drug targets in malaria treatment. In addition, some of the P. falciparum stage-specific altered proteins and parasite-host interactions might play important roles in pathogenicity, survival, invasion, and metabolic pathways and thus serve as potential source of drug targets. In this review, we have identified several proteins including thioredoxin reductase, helicases, peptidyl-prolyl cis-trans isomerase, endoplasmic reticulum-resident calcium-binding protein, choline/ethanolamine phosphotransferase, purine nucleoside phosphorylase, apical membrane antigen 1, glutamate dehydrogenase, hypoxanthine guanine phosphoribosyl transferase, heat shock protein70x, knob-associated histidine-rich protein, and erythrocyte membrane protein 1 as promising antimalarial drugs targets. Overall, proteomic approaches are able to partially facilitate finding the possible drug targets. However, the integration of other ‘omics’ and specific pharmaceutical techniques with proteomics may increase the therapeutic properties of the critical proteins identified in P. falciparum proteome.

Recombinant putative glutathione reductase of Plasmodium falciparum exhibits thioredoxin reductase activity

1996 ◽  
Vol 80 (2) ◽  
pp. 215-219 ◽  
Author(s):  
Sylke Müller ◽  
Tim-Wolf Gilberger ◽  
Petra M. Färber ◽  
Katja Becker ◽  
R. Heiner Schirmer ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Glutathione Reductase ◽  
Reductase Activity ◽  
Thioredoxin Reductase

Crystal Structure of the Plasmodium falciparum Thioredoxin Reductase–Thioredoxin Complex

2013 ◽  
Vol 425 (18) ◽  
pp. 3446-3460 ◽  
Author(s):  
Karin Fritz-Wolf ◽  
Esther Jortzik ◽  
Michaela Stumpf ◽  
Janina Preuss ◽  
Rimma Iozef ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Plasmodium Falciparum ◽  
Thioredoxin Reductase

Crystal structure of Plasmodium falciparum thioredoxin reductase, a validated drug target

2012 ◽  
Vol 425 (4) ◽  
pp. 806-811 ◽  
Author(s):  
Giovanna Boumis ◽  
Giorgio Giardina ◽  
Francesco Angelucci ◽  
Andrea Bellelli ◽  
Maurizio Brunori ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Plasmodium Falciparum ◽  
Drug Target ◽  
Thioredoxin Reductase

scholarly journals A “Seleno Effect” Differentiates the Roles of Redox Active Cysteine Residues in Plasmodium falciparum Thioredoxin Reductase

Biochemistry ◽  
2018 ◽  
Vol 57 (11) ◽  
pp. 1767-1778 ◽  
Author(s):  
John P. O’Keefe ◽  
Christopher M. Dustin ◽  
Drew Barber ◽  
Gregg W. Snider ◽  
Robert J. Hondal
Keyword(s):  
Plasmodium Falciparum ◽  
Thioredoxin Reductase ◽  
Cysteine Residues ◽  
Redox Active ◽  
Redox Active Cysteine

scholarly journals Eosin B as a Novel Antimalarial Agent for Drug-Resistant Plasmodium falciparum

2006 ◽  
Vol 50 (9) ◽  
pp. 3132-3141 ◽  
Author(s):  
Kristen M. Massimine ◽  
Michael T. McIntosh ◽  
Lanxuan T. Doan ◽  
Chloé E. Atreya ◽  
Stephan Gromer ◽  
...  
Keyword(s):  
Cell Culture ◽  
Plasmodium Falciparum ◽  
Thioredoxin Reductase ◽  
Cross Resistance ◽  
Drug Resistant ◽  
Eosin B ◽  
Folate Biosynthesis ◽  
Intracellular Organelles ◽  
Red Dye

ABSTRACT 4′,5′-Dibromo-2′,7′-dinitrofluorescein, a red dye commonly referred to as eosin B, inhibits Toxoplasma gondii in both enzymatic and cell culture studies with a 50% inhibitory concentration (IC50) of 180 μM. As a non-active-site inhibitor of the bifunctional T. gondii dihydrofolate reductase-thymidylate synthase (DHFR-TS), eosin B offers a novel mechanism for inhibition of the parasitic folate biosynthesis pathway. In the present study, eosin B was further evaluated as a potential antiparasitic compound through in vitro and cell culture testing of its effects on Plasmodium falciparum. Our data revealed that eosin B is a highly selective, potent inhibitor of a variety of drug-resistant malarial strains, with an average IC50 of 124 nM. Furthermore, there is no indication of cross-resistance with other clinically utilized compounds, suggesting that eosin B is acting via a novel mechanism. The antimalarial mode of action appears to be multifaceted and includes extensive damage to membranes, the alteration of intracellular organelles, and enzymatic inhibition not only of DHFR-TS but also of glutathione reductase and thioredoxin reductase. In addition, preliminary studies suggest that eosin B is also acting as a redox cycling compound. Overall, our data suggest that eosin B is an effective lead compound for the development of new, more effective antimalarial drugs.

scholarly journals The role of the C-terminus for catalysis of the large thioredoxin reductase from Plasmodium falciparum

FEBS Letters ◽  
1998 ◽  
Vol 425 (3) ◽  
pp. 407-410 ◽  
Author(s):  
Tim-Wolf Gilberger ◽  
Bärbel Bergmann ◽  
Rolf D Walter ◽  
Sylke Müller
Keyword(s):  
Plasmodium Falciparum ◽  
Thioredoxin Reductase ◽  
C Terminus

scholarly journals Important Docking study of Structure of Plasmodium falciparum thioredoxin reductase-thioredoxin complex: the case of potent drug Telatinib, a small molecule angiogenesis inhibitor

2021 ◽  
Author(s):  
Ivan Vito Ferrari
Keyword(s):  
Plasmodium Falciparum ◽  
Tyrosine Kinases ◽  
Drug Targets ◽  
Redox Homeostasis ◽  
Angiogenesis Inhibitor ◽  
Thioredoxin Reductase ◽  
Docking Study ◽  
Autodock Vina ◽  
Potent Drug ◽  
Novel Drug

Background: Over the last decades, malaria parasites have been rapidly developing resistance against antimalarial drugs, which underlines the need for novel drug targets. Thioredoxin reductase (TrxR) is crucially involved in redox homeostasis and essential for Plasmodium falciparum. In this communication, we report first time important Docking study by in Silico approach, using AutoDock Vina. After a selective analysis of over 300 drugs, processed with Pyrx (a Virtual Screening software into the active site of protein (ID PDB 4J56 Thioredoxin reductase 2 Chain A), we noticed excellent value of Binding Energy of Telatinib estimated by Pyrx software. These results are comparable to the crystallized ligand FAD (FLAVIN-ADENINE DINUCLEOTIDE) completed in the above-mentioned protein. Indeed, from the results of Autodock Vina, Telatinib an inhibitor of tyrosine kinases, has excellent a Binding affinity value, ca. -12 kcal/mol.

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