A replicative in vitro assay for drug discovery against Leishmania donovani.


Tegazzini, D; Díaz, R; Aguilar, F; Peña, I; Presa, JL; Yardley, V; Martin, JJ; Coteron, JM; Croft, SL; Cantizani, J; (2016) A replicative in vitro assay for drug discovery against Leishmania donovani. Antimicrobial agents and chemotherapy, 60 (6). pp. 3524-32. ISSN 0066-4804 DOI: 10.1128/AAC.01781-15

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Abstract

: The protozoan parasite Leishmania donovani is the causative agent of visceral leishmaniasis, a disease potentially fatal if not treated. Current available treatments have major limitations, and new and safer drugs are urgently needed. In recent years, advances in high-throughput screening technologies have enabled the screening of millions of compounds to identify new antileishmanial agents. However, most of the compounds identified in vitro did not translate their activities when tested in in vivo models, highlighting the need to develop more predictive in vitro assays. In the present work, we describe the development of a robust replicative, high-content, in vitro intracellular L. donovani assay. Horse serum was included in the assay media to replace standard fetal bovine serum, to completely eliminate the extracellular parasites derived from the infection process. A novel phenotypic in vitro infection model has been developed, complemented with the identification of the proliferation of intracellular amastigotes measured by EdU incorporation. In vitro and in vivo results for miltefosine, amphotericin B, and the selected compound 1 have been included to validate the assay.<br/>

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Antimicrobial Resistance Centre (AMR)
Leishmaniasis Group
Neglected Tropical Diseases Network
PubMed ID: 27021313
Web of Science ID: 377048900032
URI: http://researchonline.lshtm.ac.uk/id/eprint/2535797

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