edoc

Repurposing of anticancer drugs: in vitro and in vivo activities against Schistosoma mansoni

Cowan, Noemi and Keiser, Jennifer. (2015) Repurposing of anticancer drugs: in vitro and in vivo activities against Schistosoma mansoni. Parasites and Vectors, 8. p. 417.

[img]
Preview
PDF - Published Version
Available under License CC BY (Attribution).

689Kb

Official URL: http://edoc.unibas.ch/dok/A6420000

Downloads: Statistics Overview

Abstract

BACKGROUND: Drug discovery for the neglected tropical disease schistosomiasis has a high priority. Anticancer drugs, especially protein kinase inhibitors, might serve as a starting point for drug discovery owing to the importance of protein kinases in helminth growth and development. Furthermore, the Schistosoma mansoni genome encodes several genes for targets of drugs marketed for human use, including several anticancer drugs.
METHODS: In this study, we screened the approved oncology drug set of the National Cancer Institute's Developmental Therapeutic Program for antischistosomal activity. Drugs were tested in vitro against the larval and adult stage of S. mansoni. IC50 values and albumin binding were determined for active compounds. Lead compounds were tested in the chronic S. mansoni mouse model.
RESULTS: Eleven of the 114 compounds tested revealed IC50 values ≤ 10 μM against both S. mansoni stages. Five of these lost activity against adult S. mansoni in the presence of serum albumin. Of 6 compounds studied in vivo, the highest activity was observed from two kinase inhibitors trametinib, and vandetanib, which reduced worm burden by 63.6 and 48.1% respectively, after a single oral dose of 400 mg/kg body weight.
CONCLUSION: Our study has confirmed that oncology drugs possess antischistosomal activity. There is space for further investigation, including elucidation of the mechanisms of action of schistosome-active cancer drugs, application of different treatment courses, and structure-activity relationship studies for improving drug potency.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Helminth Drug Development (Keiser)
UniBasel Contributors:Keiser, Jennifer
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:BioMed Central
e-ISSN:1756-3305
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:15 Nov 2016 15:34
Deposited On:04 Sep 2015 14:30

Repository Staff Only: item control page