What question did this study set out to answer?

To identify novel parasiticidal drug candidates for the treatment of alveolar echinococcosis by screening the open-source Medicines for Malaria Venture Malaria Box.

March 11, 2016PLoS neglected tropical diseasesOpen Access

Screening of the Open Source Malaria Box Reveals an Early Lead Compound for the Treatment of Alveolar Echinococcosis

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Authors

BLBritta Lundström‐Stadelmann RRReto Rufener DADenise Aeschbacher

Discussion

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Overview

Preclinical drug screening demonstrates potent in vitro parasiticidal activity of salicylanilide MMV665807 against Echinococcus multilocularis, highlighting in vivo efficacy hurdles in mice.

Key Points

To identify novel parasiticidal drug candidates for the treatment of alveolar echinococcosis by screening the open-source Medicines for Malaria Venture Malaria Box.
Screened 400 antimalarial compounds at 10 μM and 1 μM against Echinococcus multilocularis metacestodes using a phosphoglucose isomerase (PGI) viability assay.
Evaluated mammalian cytotoxicity in human foreskin fibroblasts and Reuber rat hepatoma cells, followed by ultrastructural analysis via electron microscopy.
Assessed in vivo efficacy of the lead compound in mice experimentally infected with E. multilocularis metacestodes via oral and intraperitoneal routes.
Primary screening identified 24 active compounds at 10 μM, with two molecules—MMV665807 and MMV665794—achieving an EC50 below 5 μM.
The salicylanilide MMV665807 demonstrated selective metacestode toxicity over mammalian cells and direct parasiticidal activity against isolated germinal layer cells.
Oral and intraperitoneal administration of MMV665807 in infected mice produced no reduction in parasite load compared to untreated controls.

Cite This Study

Lundström‐Stadelmann et al. (2016) studied this question.

synapsesocial.com/papers/6a9054bd7b6e700e2c8a4e44 https://doi.org/10.1371/journal.pntd.0004535

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March 11, 2016PLoS neglected tropical diseasesOpen Access

Screening of the Open Source Malaria Box Reveals an Early Lead Compound for the Treatment of Alveolar Echinococcosis

View Full Paper

Ask AI

Bookmark

Authors

BLBritta Lundström‐Stadelmann RRReto Rufener DADenise Aeschbacher

Discussion

Member takes

Overview

Preclinical drug screening demonstrates potent in vitro parasiticidal activity of salicylanilide MMV665807 against Echinococcus multilocularis, highlighting in vivo efficacy hurdles in mice.

Key Points

To identify novel parasiticidal drug candidates for the treatment of alveolar echinococcosis by screening the open-source Medicines for Malaria Venture Malaria Box.
Screened 400 antimalarial compounds at 10 μM and 1 μM against Echinococcus multilocularis metacestodes using a phosphoglucose isomerase (PGI) viability assay.
Evaluated mammalian cytotoxicity in human foreskin fibroblasts and Reuber rat hepatoma cells, followed by ultrastructural analysis via electron microscopy.
Assessed in vivo efficacy of the lead compound in mice experimentally infected with E. multilocularis metacestodes via oral and intraperitoneal routes.
Primary screening identified 24 active compounds at 10 μM, with two molecules—MMV665807 and MMV665794—achieving an EC50 below 5 μM.
The salicylanilide MMV665807 demonstrated selective metacestode toxicity over mammalian cells and direct parasiticidal activity against isolated germinal layer cells.
Oral and intraperitoneal administration of MMV665807 in infected mice produced no reduction in parasite load compared to untreated controls.

Cite This Study

Lundström‐Stadelmann et al. (2016) studied this question.

synapsesocial.com/papers/6a9054bd7b6e700e2c8a4e44 https://doi.org/10.1371/journal.pntd.0004535

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