Drug discovery for Chagas disease: Impact of different host cell lines on assay performance and hit compound selection

by Franco CH, Alcântara LM, Chatelain E, Freitas-Junior L, Borsoi Moraes C. Tropical Medicine and Infectious Disease 2019, 4(82). doi: 10.3390/tropicalmed4020082

Summary: Several different cell lines have been used as host cells in cell-based screening, the main strategy for testing compounds in Chagas disease drug discovery. The authors investigate the role of host cell characteristics when assessing anti-T. cruzi compound activity, as this ultimately impacts hit discovery. Rates of infection and susceptibility to benznidazole varied between the four distinct mammalian cell lines (U2OS, THP-1, Vero, and L6) used as T. cruzi host cells. A library of 1,280 compounds was screened against the four different T. cruzi infected cell lines, resulting in 82 distinct hits, two of which were common to all four cell lines. One of the selected hits, compound FPL64176, was selective for T. cruzi and could be a starting point for the discovery of new drugs for Chagas disease.

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