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Drug Discovery for Chagas Disease: Impact of Different Host Cell Lines on Assay Performance and Hit Compound Selection
- Source :
- Tropical Medicine and Infectious Disease; Volume 4; Issue 2; Pages: 82, Tropical Medicine and Infectious Disease, Tropical Medicine and Infectious Disease, Vol 4, Iss 2, p 82 (2019)
- Publication Year :
- 2019
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2019.
-
Abstract
- Cell-based screening has become the major compound interrogation strategy in Chagas disease drug discovery. Several different cell lines have been deployed as host cells in screening assays. However, host cell characteristics and host-parasite interactions may play an important role when assessing anti-T. cruzi compound activity, ultimately impacting on hit discovery. To verify this hypothesis, four distinct mammalian cell lines (U2OS, THP-1, Vero and L6) were used as T. cruzi host cells in High Content Screening assays. Rates of infection varied greatly between different host cells. Susceptibility to benznidazole also varied, depending on the host cell and parasite strain. A library of 1,280 compounds was screened against the four different cell lines infected with T. cruzi, resulting in the selection of a total of 82 distinct compounds as hits. From these, only two hits were common to all four cell lines assays (2.4%) and 51 were exclusively selected from a single assay (62.2%). Infected U2OS cells were the most sensitive assay, as 55 compounds in total were identified as hits; infected THP-1 yielded the lowest hit rates, with only 16 hit compounds. Of the selected hits, compound FPL64176 presented selective anti-T. cruzi activity and could serve as a starting point for the discovery of new anti-chagasic drugs.
- Subjects :
- 0301 basic medicine
Chagas disease
Phenotypic screening
Trypanosoma cruzi
030106 microbiology
Cell
chagas disease drug discovery
lcsh:Medicine
Biology
Article
03 medical and health sciences
medicine
host cells
General Immunology and Microbiology
high content screening
Drug discovery
lcsh:R
phenotypic screening
Public Health, Environmental and Occupational Health
host-parasite interactions
medicine.disease
biology.organism_classification
Virology
030104 developmental biology
Infectious Diseases
medicine.anatomical_structure
Cell culture
Benznidazole
High-content screening
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 24146366
- Database :
- OpenAIRE
- Journal :
- Tropical Medicine and Infectious Disease; Volume 4; Issue 2; Pages: 82
- Accession number :
- edsair.doi.dedup.....0f6a0e1644904b7564f4337743ad5a36
- Full Text :
- https://doi.org/10.3390/tropicalmed4020082