Acanthamoeba castellanii Neff: In vitro activity against the trophozoite stage of a natural sesquiterpene and a synthetic cobalt(II)–lapachol complex

Martín-Navarro, Carmen M.; López-Arencibia, Atteneri; Lorenzo‐Morales, Jacob; Oramas‐Royo, Sandra; Hernández-Molina, Rita; Estévez‐Braun, Ana; Ravelo, Ángel G.; Valladares, Basilio; Piñero, José E.

doi:10.1016/j.exppara.2009.12.015

Cited by 27 publications

(13 citation statements)

References 17 publications

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“…The anti-Acanthamoeba activities of the assayed drugs were determined by the alamarBlue assay, as previously described (5,34,35). Briefly, Acanthamoeba trophozoites were seeded into a 96-well microtiter plate with 50 l from a stock solution of 8 ϫ 10 4 cells/ml.…”

Section: Loftus Personal Communication)mentioning

confidence: 99%

Inhibition of 3-Hydroxy-3-Methylglutaryl–Coenzyme A Reductase and Application of Statins as a Novel Effective Therapeutic Approach against Acanthamoeba Infections

Martín-Navarro

Lorenzo‐Morales

Machín

et al. 2013

Antimicrob Agents Chemother

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f Acanthamoeba is an opportunistic pathogen in humans, whose infections most commonly manifest as Acanthamoeba keratitis or, more rarely, granulomatous amoebic encephalitis. Although there are many therapeutic options for the treatment of Acanthamoeba, they are generally lengthy and/or have limited efficacy. Therefore, there is a requirement for the identification, validation, and development of novel therapeutic targets against these pathogens. Recently, RNA interference (RNAi) has been widely used for these validation purposes and has proven to be a powerful tool for Acanthamoeba therapeutics. Ergosterol is one of the major sterols in the membrane of Acanthamoeba. 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase is an enzyme that catalyzes the conversion of HMG-CoA to mevalonate, one of the precursors for the production of cholesterol in humans and ergosterol in plants, fungi, and protozoa. Statins are compounds which inhibit this enzyme and so are promising as chemotherapeutics. In order to validate whether this enzyme could be an interesting therapeutic target in Acanthamoeba, small interfering RNAs (siRNAs) against HMG-CoA were developed and used to evaluate the effects induced by the inhibition of Acanthamoeba HMG-CoA. It was found that HMG-CoA is a potential drug target in these pathogenic free-living amoebae, and various statins were evaluated in vitro against three clinical strains of Acanthamoeba by using a colorimetric assay, showing important activities against the tested strains. We conclude that the targeting of HMG-CoA and Acanthamoeba treatment using statins is a novel powerful treatment option against Acanthamoeba species in human disease.

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Section: Loftus Personal Communication)mentioning

confidence: 99%

Inhibition of 3-Hydroxy-3-Methylglutaryl–Coenzyme A Reductase and Application of Statins as a Novel Effective Therapeutic Approach against Acanthamoeba Infections

Martín-Navarro

Lorenzo‐Morales

Machín

et al. 2013

Antimicrob Agents Chemother

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“…After the study of the amoebicidal and cytoxic activity of the drugs, squaramides 3 and 5 and polyamine 6 were selected to be tested against A. castellanii cysts, which are less susceptible to the treatments than are trophozoites. Although in many recent publications on chemotherapy against Acanthamoeba, [15] The results showed that no cysts reverted to trophozoites with chlorhexidine digluconate and compound 3, (Figure 3 [32]. However, it is difficult to believe that a chemical destroying the membrane of the amoeba would not at the same time affect the plasma membranes of the ocular cells, and it has been demonstrated that with continued medical treatment, the iris and lens cells die, and cataracts develop [45].…”

Section: Resultsmentioning

confidence: 97%

“…AlamarBlue Assay Reagent® was used in order to determine the A. castellanii anti-trophozoite activity of the squaramides and acyclic polyamines as previously described [15] [31] with some modifications.Assays were conducted using a 96-well microtiter plate (Sigma, Aldrich). Briefly, 1 × 10 4 trophozoites, in 100 µl of CGV medium with 10% inactivated fetal bovine serum, were seeded in the microtiter plates and were allowed to adhere for incubation 1 h at 28˚C.…”

Section: In Vitro Amoebicidal Assaysmentioning

confidence: 99%

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<i>In Vitro</i> Activity of Squaramides and Acyclic Polyamine Derivatives against Trophozoites and Cysts of <i>Acanthamoeba castellanii</i>

Rosales¹,

Ximenis²,

Costa³

et al. 2018

JBM

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Pathogenic strains of Acanthamoeba cause keratitis (AK), granulomatous amoebic encephalitis (GAE), amoebic pneumonitis (AP), and skin infection in human and animals. The treatment of an Acanthamoeba infection is invariably very difficult and not always effective, and compounds that are amebicidic or amebistatic are frequently toxic and/or irritating for humans. Squaramides and polyamine derivatives have been demonstrated to have antitumor and antiprotozoal activity. The aim of this study was to investigate the activity of 5 squaramides and 5 acyclic polyamines against trophozoites and cysts of A. castellanii Neff. Amoebicidal activity against the trophozoites and cytotoxicity against Vero cells were evaluated with a colorimetric assay, using Alamar Blue®, and chlorhexidine digluconate was assayed as the reference drug. The squaramides 3 and 5 and the acyclic polyamine 6 appeared to be the most active against the trophozoites and their cytotoxicity was low, showing selectivity indexes of 28.3, 26, and 25.7, respectively, similar to the control drug, chlorhexidine digluconate (27.6). But only the squaramide 3 showed complete cysticidal activity at the concentrations of 100 and 200 µM, as the chlorhexidine digluconate. Further studies of the mechanism of action and in vivo assays are needed, but squaramide 3 could be used for developing novel therapeutic approaches against Acanthamoeba infections.

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“…The amoebicidal activity found in the P. polystachyum essential oil could be occurring by the action of specific compounds within the oil or the synergistic action of several molecules. A study of Martín-Navarro et al (2010) showed that the α-cyperotundone, a natural sesquiterpene isolated from the root bark of Maytenus retusa, was able to inhibit the in vitro growth of the amoebae at relatively low concentrations. However, the identification of the molecular targets of this sesquiterpene and its effects on Acanthamoeba has yet to be discovered.…”

Section: Discussionmentioning

confidence: 99%

Amoebicidal activity and chemical composition of Pterocaulon polystachyum (Asteraceae) essential oil

Sauter¹,

Santos

Apel

et al. 2011

Parasitol Res

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Acanthamoeba species are free-living amoebae that constitute an etiological agent of Acanthamoeba keratitis, an illness that may cause severe ocular inflammation and blindness and has a very difficult treatment. These molecules that are found in plants may be an alternative for the development of new drugs. Plants of the genus Pterocaulon (Asteraceae) are used in folk medicine as an antiseptic and antifungal agent. In this work, we analyzed Pterocaulon polystachyum essential oil and assessed its amoebicidal activity against Acanthamoeba polyphaga. The leaves of the fresh plant submitted to hydrodistillation yielded 0.15% (w/v) of essential oil that was analyzed by gas chromatography-mass spectrometry being E-sesquilavandulyl acetate as the major component, representing 43.8% of the oil. For the assessment of the amoebicidal activity, concentrations of 20, 10, 5, 2.5, and 1.25 mg/mL of essential oil were tested, being lethal to 100% of the A. polyphaga trophozoites at the concentrations of 10 and 20 mg/mL in 24 and 48 h. The cytotoxic effect of essential oil was also tested in mammalian cells using MTT assay. Amoebicidal activity results are in accordance with previous work in which the lipophilic compounds from this plant were active against Acanthamoeba castellanii. However, further studies with the major component of the essential oil will be carried out.

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Acanthamoeba castellanii Neff: In vitro activity against the trophozoite stage of a natural sesquiterpene and a synthetic cobalt(II)–lapachol complex

Cited by 27 publications

References 17 publications

Inhibition of 3-Hydroxy-3-Methylglutaryl–Coenzyme A Reductase and Application of Statins as a Novel Effective Therapeutic Approach against Acanthamoeba Infections

Inhibition of 3-Hydroxy-3-Methylglutaryl–Coenzyme A Reductase and Application of Statins as a Novel Effective Therapeutic Approach against Acanthamoeba Infections

<i>In Vitro</i> Activity of Squaramides and Acyclic Polyamine Derivatives against Trophozoites and Cysts of <i>Acanthamoeba castellanii</i>

Amoebicidal activity and chemical composition of Pterocaulon polystachyum (Asteraceae) essential oil

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Acanthamoeba castellanii Neff: In vitro activity against the trophozoite stage of a natural sesquiterpene and a synthetic cobalt(II)–lapachol complex

Cited by 27 publications

References 17 publications

Inhibition of 3-Hydroxy-3-Methylglutaryl–Coenzyme A Reductase and Application of Statins as a Novel Effective Therapeutic Approach against Acanthamoeba Infections

Inhibition of 3-Hydroxy-3-Methylglutaryl–Coenzyme A Reductase and Application of Statins as a Novel Effective Therapeutic Approach against Acanthamoeba Infections

&lt;i&gt;In Vitro&lt;/i&gt; Activity of Squaramides and Acyclic Polyamine Derivatives against Trophozoites and Cysts of &lt;i&gt;Acanthamoeba castellanii&lt;/i&gt;

Amoebicidal activity and chemical composition of Pterocaulon polystachyum (Asteraceae) essential oil

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<i>In Vitro</i> Activity of Squaramides and Acyclic Polyamine Derivatives against Trophozoites and Cysts of <i>Acanthamoeba castellanii</i>