Identification of small-molecule inhibitors of ricin and shiga toxin using a cell-based high-throughput screen.

ABSTRACT: The Category B agents, ricin and shiga toxin (Stx), are RNA N-glycosidases that target a highly conserved adenine residue within the sarcin-ricin loop of eukaryotic 28S ribosomal RNA. In an effort to identify small-molecule inhibitors of these toxins that could serve as lead compounds for potential therapeutics, we have developed a simple Vero cell-based high-throughput cytotoxicity assay and have used it to screen approximately 81,300 compounds in 17 commercially available chemical libraries. This initial screen identified approximately 300 compounds with weak (>or=30 to <50%), moderate (>or=50 to <80%), or strong (>or=80%) ricin inhibitory activity. Secondary analysis of 244 of these original "hits" was performed, and 20 compounds that were capable of reducing ricin cytotoxicity by >50%

SUBMITTER: Wahome PG 

PROVIDER: S-EPMC2902711 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature