Anti-Tuberculosis Drug Discovery by Bioluminescence-Based Screening of a Protein Kinase Inhibitor Library
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Abstract
A library of 3000 putative kinase inhibitors from the ChemBridge Corporation was first screened by bioluminescence assay against Mycobacterium smegmatis, a non-virulent model organism for Mycobacterium tuberculosis (M.tb), to identify compounds which could successfully inhibit the growth of M.tb. After screening against a M. smegmatis reporter strain expressing luciferase, we found nine compounds which significantly inhibited its growth, as indicated by lower relative luminescence units (RLUs) over time. These nine compounds were tested in a similar fashion for their effects on M.tb growth in both in-vitro broth culture and inside human macrophages. From this bio-screening analysis, two compounds, 14/C5 and 17/G7, were identified as having the most effect on M.tb growth and considered as promising anti-tuberculosis (anti-TB) drugs for further analysis.