Ionophore Properties of Monensin Derivatives Studied on Human Erythrocytes by 23Na NMR and K+ and H+ Potentiometry:  Relationship with Antimicrobial and Antimalarial Activities

Rochdi, Mohamed; Delort, Anne-Marie; Guyot, J.; Sancelme, Martine; Gibot, Sylvie; Gourcy, Jean-Gabriel; Dauphin, G.; Gumila, Catherine; Vial, Henri; Jeminet, Georges

doi:10.1021/jm9505829

Cited by 36 publications

(20 citation statements)

References 36 publications

(95 reference statements)

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“…Notably, monensin has potent in vitro and in vivo antimalarial activity [60,61]. Eight derivatives of monensin showed potential antimalarial properties in the nanomolar range when tested in vitro against Plasmodium falciparum [62]. The antimalarial effect may be partially due to accelerated suicidal death and clearance of parasitized erythrocytes [63].…”

Section: Discussionmentioning

confidence: 99%

Monensin Induced Suicidal Erythrocyte Death

Bhavsar

Eberhard

Bobbala

et al. 2010

Cell Physiol Biochem

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Eryptosis, the suicidal erythrocyte death, is characterized by cell membrane scrambling and cell shrinkage. Eryptosis may be triggered by excessive hyperosmotic or isosmotic cell shrinkage leading to increase of cytosolic Ca²⁺ concentration. Eryptosis is further stimulated by the K⁺ ionophore valinomycin, which leads to exit of KCl and osmotically obliged water, or by energy (glucose) depletion, which compromises the function of the Na⁺/K⁺ ATPase thus increasing cytosolic Na⁺ concentration. The present study explored whether the Na⁺ ionophore monensin affects erythrocyte cell volume and eryptosis. The cell membrane scrambling was estimated from binding of annexin V to phosphatidylserine at the erythrocyte surface, cell volume from forward scatter in FACS analysis, cytosolic Ca²⁺ concentration from Fluo3 fluorescence and the cytosolic ATP concentration from a luciferase-based assay. Within 24 hours, exposure to monensin (0.1-10 µg/ml) significantly increased forward scatter, cytosolic Ca²⁺ concentration and annexin V-binding. Glucose depletion was followed by decreased forward scatter and increased cytosolic Ca²⁺ concentration and annexin V-binding. The effect on forward scatter was partially reversed, the effect on cytosolic Ca²⁺ concentration and annexin V binding augmented by additional treatment with monensin. In conclusion, monensin dissociates the alterations of cell membrane and cell volume in suicidal erythrocyte death.

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Section: Discussionmentioning

confidence: 99%

Monensin Induced Suicidal Erythrocyte Death

Bhavsar

Eberhard

Bobbala

et al. 2010

Cell Physiol Biochem

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“…Rochdi etal. [63] have demonstrated that 2d and 2e monensin derivatives cause an increase in the effective transport of potassium cation through the membrane, whereas there is a decrease in the transport of sodium cations. Thus, these derivatives preferentially complex and transport potassium cations prior to sodium cations.…”

Section: Monensin a Derivatives And Their Antimicrobial Activitymentioning

confidence: 99%

Structure and Antimicrobial Properties of Monensin A and Its Derivatives: Summary of the Achievements

Łowicki

Huczyński

2013

BioMed Research International

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In this paper structural and microbiological studies on the ionophorous antibiotic monensin A and its derivatives have been collected. Monensin A is an ionophore which selectively complexes and transports sodium cation across lipid membranes, and therefore it shows a variety of biological properties. This antibiotic is commonly used as coccidiostat and nonhormonal growth promoter. The paper focuses on both the latest and earlier achievements concerning monensin A antimicrobial activity. The activities of monensin derivatives, including modifications of hydroxyl groups and carboxyl group, are also presented.

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“…Monensin activity against the blood stage of P. falciparum has been described in vitro with IC50 of 1.1 nM (Adovelande and Schrevel, 1996), 1.4 nM (Gibot et al, 1999), 2.1 nM (Gumila et al, 1997) and 2.3 nM, (Rochdi et al, 1996). A recent screening of drugs predicted by molecular topology has also found monensin inhibitory activity against the liver stage of P. yoelii and P. falciparum in vitro (Mahmoudi et al, 2008).…”

Section: Inhibition Of Liver Infection In Mice By a Single Injection mentioning

confidence: 99%

Inhibition of Plasmodium sporozoites infection by targeting the host cell

Leitao

Rodrı́guez

2010

Experimental Parasitology

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There is a great need of new drugs against malaria because of the increasing spread of parasite resistance against the most commonly used drugs in the field. We found that monensin, a common veterinary antibiotic, has a strong inhibitory effect in Plasmodium berghei and P. yoelii sporozoites hepatocyte infection in vitro. Infection of host cells by another apicomplexan parasite with a similar mechanism of host cell invasion, Toxoplasma tachyzoites, was also inhibited. Treatment of mice with monensin abrogates liver infection with P. berghei sporozoites in vivo. We also found that at low concentrations monensin inhibits the infection of Plasmodium sporozoites by rendering host cells resistant to infection, rather than having a direct effect on sporozoites. Monensin effect is targeted to the initial stages of parasite invasion of the host cell with little or no effect on development, suggesting that this antibiotic affects an essential host cell component that is required for Plasmodium sporozoite invasion.Malaria, one of the most important parasitic diseases in humans, remains one of the major infectious diseases worldwide (Fauci, 2008). Considering the increasing problem of drug resistance in the parasite, there is an urgent need to identify new molecules with antimalarial activity. Since malaria affects mainly populations in developing countries who cannot afford most available treatments, the cost effectiveness analysis should be one prevalent paradigm taken into consideration when developing novel antimalarial therapies.The liver stage is the initial step of natural malaria infection in mammals, which is initiated when a mosquito inoculates Plasmodium sporozoites into the skin of the host. The sporozoites migrate in the dermis, reach blood vessels and are carried rapidly via the bloodstream to the liver, where they invade hepatic parenchymal cells and begin a period of asexual reproduction, producing exo-erythrocytic forms (EEFs) (Ejigiri and Sinnis, 2009). Upon maturation, infected hepatocytes release merozoites that invade erythrocytes, initiating the blood stage of the disease. Inhibitors of Plasmodium growth in the liver assume a particular relevance as prophylactic agents, but the list of applied drugs is very limited (Fauci, 2008).Monensin is a Na + ionophore that exchanges specifically Na + for H + , resulting in elevated cytosolic Na + concentration and pH (Mollenhauer et al., 1990 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptSpreptomyces cinnamonensis, is a w...

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Ionophore Properties of Monensin Derivatives Studied on Human Erythrocytes by ²³Na NMR and K⁺and H⁺ Potentiometry: Relationship with Antimicrobial and Antimalarial Activities

Cited by 36 publications

References 36 publications

Monensin Induced Suicidal Erythrocyte Death

Monensin Induced Suicidal Erythrocyte Death

Structure and Antimicrobial Properties of Monensin A and Its Derivatives: Summary of the Achievements

Inhibition of Plasmodium sporozoites infection by targeting the host cell

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