Abstract
A small library of pyrrolidinesulphonylaryl molecules has been synthesized via an efficient 4-step route, and members evaluated for their ability to inhibit IL-6 signalling. One molecule (6a) was found to have promising activity against IL-6/STAT3 signalling at the low micromolar level, and to selectively inhibit phosphorylation of STAT3 (but not STAT1) in IL-6 stimulated MDA-MB-231 breast cancer and HeLa cell lines. It was also selectively cytostatic in MDA-MB-231 (STAT3-dependent) versus A4 (STAT3-null) cells suggesting STAT3-specific inhibitory properties.
Copyright © 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Breast Neoplasms / drug therapy
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Breast Neoplasms / pathology
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Cell Line, Tumor
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Cytostatic Agents / chemistry*
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Cytostatic Agents / pharmacology
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Female
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HeLa Cells
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Humans
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Interleukin-6 / antagonists & inhibitors*
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Phosphorylation / drug effects
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Pyrrolidines / chemistry*
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Pyrrolidines / pharmacology
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STAT3 Transcription Factor / metabolism
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Signal Transduction / drug effects*
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Small Molecule Libraries
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Structure-Activity Relationship
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Sulfones
Substances
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Cytostatic Agents
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Interleukin-6
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Pyrrolidines
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STAT3 Transcription Factor
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Small Molecule Libraries
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Sulfones