期刊
JOURNAL OF BIOMOLECULAR SCREENING
卷 17, 期 7, 页码 946-956出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/1087057112448216
关键词
anti-infective drugs; automation; cell-based assays; compound repositories; high-content screening
资金
- NIH/NIAID/DMID [HHSN2662004 00004I/N01-AI-40004]
One of the objectives of the National Institutes of Allergy and Infectious Diseases (NIAID) Biodefense Program is to identify or develop broad-spectrum antimicrobials for use against bioterrorism pathogens and emerging infectious agents. As a part of that program, our institution has screened the 10 000-compound MyriaScreen Diversity Collection of high-purity druglike compounds against three NIAID category A and one category B priority pathogens in an effort to identify potential compound classes for further drug development. The effective use of a Clinical and Laboratory Standards Institute-based high-throughput screening (HTS) 96-well-based format allowed for the identification of 49 compounds that had in vitro activity against all four pathogens with minimum inhibitory concentration values of <= 16 mu g/mL. Adaptation of the HTS process was necessary to conduct the work in higher-level containment, in this case, biosafety level 3. Examination of chemical scaffolds shared by some of the 49 compounds and assessment of available chemical databases indicates that several may represent broad-spectrum antimicrobials whose activity is based on novel mechanisms of action.
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