An <i>in-vitro</i> system for determining the activity of compounds against the intracellular amastigote form of <i>Leishmania donovani</i>

Neal, R. A.; Croft, Simon L.

doi:10.1093/jac/14.5.463

Cited by 200 publications

(133 citation statements)

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“…Leishmanicidal activity against intramacrophagic amas tigotes was performed on infected mouse peritoneal macrophages according to the method of Neal & Croft (1984).…”

Section: In Vitro Evaluationmentioning

confidence: 99%

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In vivoantileishmanial action of Ir-(COD)-pentamidine tetraphenylborate onLeishmania donovaniandLeishmania majormouse models

et al. 2000

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Summary:lr-(COD)-pentamidine tetraphenylborate which has previously been studied on promastigote forms of Leishmania, was investigated for its antileishmanial properties compared with pentamidine used as reference compound. In vitro, the iridium complex had the same IC 50 value on intracellular forms of Leishmania as pentamidine (15 µM). In vivo, the compound could not be injected intravenously due to the DMSO excipient so that the treatments were performed intraperitoneally or subcutaneously. On the L. donovani LV9 /Balb/C mouse model, the iridium complex was not toxic after intraperitoneal treatment at 232 mg/kg/day x 5 or 147 µmoles/ kg/day x 5, whereas all the mice died within five days when treated at the same dose with pentamidine isethionate. However, only 23 % of parasite suppression was observed with the iridium complex. On a L. major MON 74/Balb/C mouse model, susceptible to intravenously administered pentamidine at 6.7 umoles/ kg/day x 5 (54 % of parasite suppression), the iridium complex exhibited 32 % of parasite suppression after a treatment at 76 umoles/ kg/day x 5 administered subcutaneously. This slight activity is of interest since pentamidine isethionate is not active under these conditions. Transmission electron microscopy of amastigotes from infected and treated mice show aggregation of ribosomal material, distension of the nuclear membrane and kDNA depolymerization. The mechanism of action therefore involves several targets: membranes, ribosomes and kDNA. According to our results, the Iridium complex is a suitable candidate to be encapsulated in drug carriers such as liposomes or nanoparticles.KEYWORDS : Iridium pentamidine complex, pentamidine, Leishmania, electron microscopy, mechani sm of action. MOTS CLÉS

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“…Leishmanicidal activity against intramacrophagic amas tigotes was performed on infected mouse peritoneal macrophages according to the method of Neal & Croft (1984).…”

Section: In Vitro Evaluationmentioning

confidence: 99%

“…Mice were treated once a day for five consecutive days and sacrificed three days after the end of treatment. Drug activity was estimated by counting the number of amastigotes/500 liver cells in Giemsa stained impres sion smears prepared from the weighed livers of treated and untreated mice (Neal & Croft, 1984).…”

Section: In Vivo Evaluationmentioning

confidence: 99%

In vivoantileishmanial action of Ir-(COD)-pentamidine tetraphenylborate onLeishmania donovaniandLeishmania majormouse models

et al. 2000

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“…In view of the literature precedent [11,12] and our above results with T. b. rhodesiense we decided to screen our compound library against Leishmania donovani [21]. Using HU3 intracellular amastigotes at 30 mM only 8, 9, 12 and 20 showed any activity, with 39.7, 13.8, 11.6 and 2.7% inhibition respectively.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and antitrypanosomal activities of novel pyridylchalcones

Bhambra

Ruparelia

Tan

et al. 2017

European Journal of Medicinal Chemistry

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a b s t r a c tA library of novel pyridylchalcones were synthesised and screened against Trypanosoma brucei rhodesiense. Eight were shown to have good activity with the most potent 8 having an IC 50 value of 0.29 mM.Cytotoxicity testing with human KB cells showed a good selectivity profile for this compound with a selectivity index of 47. Little activity was seen when the library was tested against Leishmania donovani. In conclusion, pyridylchalcones are promising leads in the development of novel compounds for the treatment of human African trypanosomiasis (HAT).

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“…In vitro studies have shown that paromomycin can effectively kill both promastigotes and amastigotes (Neal and Croft 1984;Gebre-Hiwot et al 1992;Neal et al 1995). The 50% effective dose (ED 50 ) of paromomycin against L. donovani amastigotes ranges from 10 to 50 lM.…”

Section: Paromomycinmentioning

confidence: 99%

Therapeutic switching in leishmania chemotherapy: a distinct approach towards unsatisfied treatment needs

2011

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Current drugs for the treatment of visceral leishmaniasis are inadequate. No novel compound is in the pipeline. Since economic returns on developing a new drug for neglected disease, leishmaniasis is so low that therapeutic switching represents the only realistic strategy. It refers to ''alternative drug use'' discoveries which differ from the original intent of the drug. Amphotericin B, paromomycin, miltefosine and many other drugs are very successful examples of ''new drugs from old''. This article reviews the discovery, growth and current status of these drugs and concluded that the potential of this approach (therapeutic switching) may use in the development of new antileishmanials in future also.

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An in-vitro system for determining the activity of compounds against the intracellular amastigote form of Leishmania donovani

Cited by 200 publications

References 0 publications

In vivoantileishmanial action of Ir-(COD)-pentamidine tetraphenylborate onLeishmania donovaniandLeishmania majormouse models

In vivoantileishmanial action of Ir-(COD)-pentamidine tetraphenylborate onLeishmania donovaniandLeishmania majormouse models

Synthesis and antitrypanosomal activities of novel pyridylchalcones

Therapeutic switching in leishmania chemotherapy: a distinct approach towards unsatisfied treatment needs

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