Cell screening assay for identifying inhibitors of eosinophil proliferation |
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| Authors: | Jessica J Kempe‐Dustin Tarek Aboul‐Fadl Clarissa Christensen Robert Palais Krishna Parsawar Gerald J Gleich Lori A Wagner |
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| Institution: | 1. Department of Dermatology, School of Medicine, University of Utah, 30 North 1900 East, Salt Lake City, UT 84132;2. Department of Pharmaceutical Chemistry, King Saud University, Riyadh, Saudi Arabia;3. Department of Pharmaceutical Medicinal Chemistry, Assiut University, Assiut, Egypt 71526;4. Department of Mathematics, University of Utah, 155 South 1400 East, Salt Lake City, UT 84132;5. Mass Spectrometry and Proteomics Core Facility, University of Utah, 20 South 2030 East, Salt Lake City, UT 84112;6. Department of Medicine, University of Utah, Salt Lake City, 30 North 1900 East, UT 84132 |
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| Abstract: | The purpose of this study was to develop a cell‐based screening assay for identification of small molecules for the treatment of asthma. Eosinophils are leukocytes that contribute to the pathology of asthma. Lidocaine inhibits interleukin‐5 (IL‐5)‐mediated survival and activation of human eosinophils, and it is able to replace inhaled glucocorticoids for the treatment of asthma; however, lidocaine has many side effects, including anesthesia. Therefore, a collection of commercial and novel, synthesized lidocaine analogues were investigated for inhibitory activity of the IL‐5‐stimulated proliferation of TF‐1 cells, a CD34+, cytokine‐dependent, erythroleukemic cell line model for eosinophil growth. Among 74 investigated compounds, 10 were more potent inhibitors of cell proliferation than lidocaine (average IC50 = 223 µM), with IC50 values ranging within 1–119 µM. This cell‐based assay is an effective method for screening chemical compounds and has revealed promising lead compounds for the treatment of asthma. Drug Dev Res 72: 353–360, 2011. © 2011 Wiley‐Liss, Inc. |
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| Keywords: | eosinophil lidocaine asthma interleukin‐5 drug |
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