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

Shakya, Nishi; Bajpai, Preeti; Gupta, Suman

doi:10.1007/s12639-011-0040-9

Cited by 20 publications

(14 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…FLU can favor the topical treatment of CL, because this drug presents high affinity for keratin prolonging its retention in the skin [ 12 ]; moreover FLU acts by inhibiting the P450 cytochrome that blocks the enzyme 14- α -demethylase, which is involved in the synthesis of the parasitic ergosterol membrane, thus helping to heal localised lesions [ 13 – 17 ].…”

Section: Introductionmentioning

confidence: 99%

Development, Characterization, andIn VitroBiological Performance of Fluconazole-Loaded Microemulsions for the Topical Treatment of Cutaneous Leishmaniasis

Oliveira

Calixto

Graminha

et al. 2015

BioMed Research International

View full text Add to dashboard Cite

Cutaneous leishmaniasis (CL) is a resistant form of leishmaniasis that is caused by a parasite belonging to the genus Leishmania. FLU-loaded microemulsions (MEs) were developed by phase diagram for topical administration of fluconazole (FLU) as prominent alternative to combat CL. Three MEs called F1, F2, and F3 (F1—60% 50 M phosphate buffer at pH 7.4 (PB) as aqueous phase, 10% cholesterol (CHO) as oil phase, and 30% soy phosphatidylcholine/oil polyoxyl-60 hydrogenated castor oil/sodium oleate (3/8/6) (S) as surfactant; F2—50% PB, 10% CHO, and 40% S; F3—40% PB, 10% CHO, and 50 % S) were characterized by droplet size analysis, zeta potential analysis, X-ray diffraction, continuous flow, texture profile analysis, and in vitro bioadhesion. MEs presented pseudoplastic flow and thixotropy was dependent on surfactant concentration. Droplet size was not affected by FLU. FLU-loaded MEs improved the FLU safety profile that was evaluated using red cell haemolysis and in vitro cytotoxicity assays with J-774 mouse macrophages. FLU-unloaded MEs did not exhibit leishmanicidal activity that was performed using MTT colourimetric assays; however, FLU-loaded MEs exhibited activity. Therefore, these MEs have potential to modulate FLU action, being a promising platform for drug delivery systems to treat CL.

show abstract

Section: Introductionmentioning

confidence: 99%

Development, Characterization, andIn VitroBiological Performance of Fluconazole-Loaded Microemulsions for the Topical Treatment of Cutaneous Leishmaniasis

Oliveira

Calixto

Graminha

et al. 2015

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…In addition, the extensive search for new drugs to treat leishmaniasis is definitely necessary because the limited number of currently available products present noticeable side effects and the resistance to these products is increasing ( Rocha et al 2005 ). Known antifungal drugs such as amphotericin B, miltefosine and azoles have also demonstrated activity against Leishmania parasites ( Moskowitz & Kurban 1999 , Tong et al 2007 , Shakya et al 2011 b). These successful results led to the development of the "therapeutic switching" or "alternative drug use" strategy ( Shakya et al.…”

mentioning

confidence: 99%

“…Known antifungal drugs such as amphotericin B, miltefosine and azoles have also demonstrated activity against Leishmania parasites ( Moskowitz & Kurban 1999 , Tong et al 2007 , Shakya et al 2011 b). These successful results led to the development of the "therapeutic switching" or "alternative drug use" strategy ( Shakya et al. 2011a ).…”

mentioning

confidence: 99%

Therapeutic switching: from antidermatophytic essential oils to new leishmanicidal products

Houël

González

Bessière

et al. 2015

Mem. Inst. Oswaldo Cruz

View full text Add to dashboard Cite

This study examined whether the antidermatophytic activity of essential oils (EOs) can be used as an indicator for the discovery of active natural products against Leishmania amazonensis. The aerial parts of seven plants were hydrodistilled. Using broth microdilution techniques, the obtained EOs were tested against three strains of dermatophytes (Trichophyton mentagrophytes, Microsporum gypseum and Microsporum canis). To compare the EOs antifungal and antiparasitic effects, the EOs activities against axenic amastigotes of L. amazonensis were concurrently evaluated. For the most promising EOs, their antileishmanial activities against parasites infecting peritoneal macrophages of BALB/c mice were measured. The most interesting antifungal candidates were the EOs from Cymbopogon citratus, Otacanthus azureus and Protium heptaphyllum, whereas O. azureus, Piper hispidum and P. heptaphyllum EOs exhibited the lowest 50% inhibitory concentration (IC50) values against axenic amastigotes, thus revealing a certain correspondence between both activities. The P. hispidum EO was identified as the most promising product in the results from the infected macrophages model (IC50: 4.7 µg/mL, safety index: 8). The most abundant compounds found in this EO were sesquiterpenes, notably curzerene and furanodiene. Eventually, the evaluation of the antidermatophytic activity of EOs appears to be an efficient method for identifying new potential drugs for the treatment of L. amazonensis.

show abstract

“…However, the number of drugs used against this disease has been enriched by compounds already used against other diseases: antifungal azoles paromomycin sulfate (Humatin ® ) amphotericin B, miltefosine [15], and different approaches have been used in order to shorten courses of therapy and reduce toxicities [16].…”

mentioning

confidence: 99%

Structural Insights into the Enzymes of the Trypanothione Pathway: Targets for Antileishmaniasis Drugs

et al. 2013

View full text Add to dashboard Cite

Leishmaniasis is a neglected disease that kills 60,000 people worldwide, and which is caused by the protozoa Leishmania. The enzymes of the trypanothione pathway: trypanothione synthetase-amidase, trypanothione reductase (TR) and tryparedoxin-dependent peroxidase are absent in human hosts, and are essential for parasite survival and druggable. The most promising target is trypanothione synthetase-amidase, which has been also chemically validated. However, the structural data presented in this review show that TR also should be considered as a good target. Indeed, it is strongly inhibited by silver- and gold-containing compounds, which are active against Leishmania parasites and can be used for the development of novel antileishmanial agents. Moreover, TR trypanothione-binding site is not featureless but contains a sub-pocket where inhibitors bind, potentially useful for the design of new lead compounds.

show abstract

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

Cited by 20 publications

References 74 publications

Development, Characterization, andIn VitroBiological Performance of Fluconazole-Loaded Microemulsions for the Topical Treatment of Cutaneous Leishmaniasis

Development, Characterization, andIn VitroBiological Performance of Fluconazole-Loaded Microemulsions for the Topical Treatment of Cutaneous Leishmaniasis

Therapeutic switching: from antidermatophytic essential oils to new leishmanicidal products

Structural Insights into the Enzymes of the Trypanothione Pathway: Targets for Antileishmaniasis Drugs

Contact Info

Product

Resources

About