Antioxidant enzyme profile of two clinical isolates of <i>Entamoeba histolytica</i> varying in sensitivity to antiamoebic drugs

Iyer, Lakshmi Rani; Banyal, Neha; Naik, Shailendra; Paul, Jaishree

doi:10.5495/wjcid.v7.i2.21

Cited by 10 publications

(11 citation statements)

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“…They are also seen to participate in protein synthesis and cell cycle regulation , maintenance of chromatin structure , and stabilization of RNA molecules . Several studies have shown an increase in the concentration of polyamine pathway enzymes and polyamines in many cancer cases . Polyamine analogs mainly with an ethyl or benzyl group attached to the terminal residues are generally used in anticancer therapeutics .…”

Section: Introductionmentioning

confidence: 99%

“…Presently, a small number of antiamoebic drugs like tinidazole, chloroquine, nitazoxanide, auranofin, and metronidazole are utilized for the cure of the disease. These antiamoebic drugs are efficient against amebiasis but are facing some challenges due to the rapid development and spread of the drug‐resistant parasites . Additionally, few of these drugs are found to possess side effects.…”

Section: Introductionmentioning

confidence: 99%

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Structural insights into Entamoeba histolytica arginase and structure‐based identification of novel non‐amino acid based inhibitors as potential antiamoebic molecules

et al. 2019

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Arginase, the binuclear metalloenzyme, is a potential target for therapeutic intervention in protozoan infections. Entamoeba histolytica infection causes amebiasis which is the second most common cause of protozoan‐related human deaths after malaria. Here, we report the crystal structure of E. histolytica arginase (EhArg) in complex with two known inhibitors Nω‐hydroxy‐l‐arginine (l‐NOHA) and l‐norvaline, and its product l‐ornithine at 1.7, 2.0, and 2.4 Å, respectively. Structural and comparative analysis of EhArg–inhibitor complexes with human arginase revealed that despite only 33% sequence identity, the structural determinants of inhibitor recognition and binding are highly conserved in arginases with variation in oligomerization motifs. Knowledge regarding the spatial organization of residues making molecular contacts with inhibitory compounds enabled in the identification of four novel non‐amino acid inhibitors, namely irinotecan, argatroban, cortisone acetate, and sorafenib. In vitro testing of the in silico‐identified inhibitors using purified enzyme proved that irinotecan, argatroban, cortisone acetate, and sorafenib inhibit EhArg with IC50 value (mm) of 1.99, 2.40, 0.91, and 2.75, respectively, as compared to the known inhibitors l‐NOHA and l‐norvaline with IC50 value (mm) of 1.57 and 17.9, respectively. The identification of structure‐based non‐amino acid inhibitory molecules against arginase will be constructive in design and discovery of novel chemical modulators for treating amebiasis by directed therapeutics.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Structural insights into Entamoeba histolytica arginase and structure‐based identification of novel non‐amino acid based inhibitors as potential antiamoebic molecules

et al. 2019

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“…E. histolytica is capable of acquiring resistance to amebicidal concentrations of metronidazole (MTZ), the current drug of choice, under laboratory conditions, and this drug resistance has been associated with an increased expression of iron-containing superoxide dismutase and peroxiredoxin (Wassmann et al, 1999). Moreover, partial resistance to MTZ has also been described in some clinical strains of E. histolytica , suggesting the emergence of MTZ resistant strains (Bansal et al, 2004; Iyer et al, 2017). Thus, these observations have led to the search for new drugs with targets and modes of action distinct from those of MTZ [for a recent review see (Nagaraja and Ankri, 2019)].…”

Section: Drug Discoverymentioning

confidence: 99%

Editorial: Recent Progresses in Amebiasis

Debnath

Rodríguez

Ankri

2019

Front. Cell. Infect. Microbiol.

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“…Globally, these mucosa-associated protozoa are one of the leading causes of morbidity and mortality, mainly in areas of intense poverty, in marginal communities of urban centres and rural areas in developing countries ( Iyer et al., 2017 ). The clinical spectrum of diseases produced by these protozoa ranges from asymptomatic (up to 50%) to severe disease, which includes liver abscesses, malabsorption syndrome, vaginitis, and urethritis ( Collaborators, 2017 ; Leung et al., 2019 ; Li et al., 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…As a result, children are more at risk for infection, and cryptosporidiosis is more prevalent in children and immunosuppressed patients. Similarly, children are more likely to have giardiasis and amebiasis than adults ( Iyer et al., 2017 ).…”

Section: Introductionmentioning

confidence: 99%

An Overview of Mucosa-Associated Protozoa: Challenges in Chemotherapy and Future Perspectives

Santos

Rebello

2022

Front. Cell. Infect. Microbiol.

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Parasitic infections caused by protozoans that infect the mucosal surfaces are widely neglected worldwide. Collectively, Entamoeba histolytica, Giardia lamblia, Cryptosporidium spp. and Trichomonas vaginalis infect more than a billion people in the world, being a public health problem mainly in developing countries. However, the exact incidence and prevalence data depend on the population examined. These parasites ultimately cause pathologies that culminate in liver abscesses, malabsorption syndrome, vaginitis, and urethritis, respectively. Despite this, the antimicrobial agents currently used to treat these diseases are limited and often associated with adverse side effects and refractory cases due to the development of resistant parasites. The paucity of drug treatments, absence of vaccines and increasing problems of drug resistance are major concerns for their control and eradication. Herein, potential candidates are reviewed with the overall aim of determining the knowledge gaps and suggest future perspectives for research. This review focuses on this public health problem and focuses on the progress of drug repositioning as a potential strategy for the treatment of mucosal parasites.

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Antioxidant enzyme profile of two clinical isolates of Entamoeba histolytica varying in sensitivity to antiamoebic drugs

Cited by 10 publications

References 0 publications

Structural insights into Entamoeba histolytica arginase and structure‐based identification of novel non‐amino acid based inhibitors as potential antiamoebic molecules

Structural insights into Entamoeba histolytica arginase and structure‐based identification of novel non‐amino acid based inhibitors as potential antiamoebic molecules

Editorial: Recent Progresses in Amebiasis

An Overview of Mucosa-Associated Protozoa: Challenges in Chemotherapy and Future Perspectives

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