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2-Guanidinoquinazolines as new inhibitors of the STAT3 pathway
Affiliation:1. University of Pittsburgh Chemical Diversity Center, University of Pittsburgh, Pittsburgh, PA 15260, USA;2. Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA 15260, USA;3. University of Pittsburgh Cancer Institute, Pittsburgh, PA 15260, USA;4. Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15260, USA;5. Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA;6. Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA;1. Department of Physiology, School of Basic Medical Sciences, Wuhan University, 185 Donghu Road, Wuhan, Hubei 430071, PR China;2. Research Triangle Institute, Research Triangle Park, NC 27709, USA;3. Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, 102 Farber Hall, Buffalo, NY 14214, USA;1. Eskitis Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia;2. Department of Botany II, Julius-von-Sachs Institute for Biological Sciences, University of Würzburg, Julius-von-Sachs-Platz 3, D-97082 Würzburg, Germany;3. Department of Toxicology, University of Würzburg, Würzburg, Germany;4. Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, The John Arbuthnott Building, 161 Cathedral Street, Glasgow G4 0NR, UK;1. School of Mechanical and Electrical Engineering, University of Southern Queensland, Toowoomba, QLD 4350, Australia;2. Computer Engineering Department, University of Mosul, Mosul, Iraq;3. Department of Electrical Engineering, University of Mississippi, University, MS 38677, USA;1. ISTRA, Department of Chemistry, MCE Society’s Abeda Inamdar Senior College of Arts, Science and Commerce, University of Pune, Pune 411001, India;2. Department of Animal Sciences, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India;3. Department of Bioinformatics and Computer Science, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune 411044, India
Abstract:Synthesis and SAR investigation of 2-guanidinoquinazolines, initially identified in a high content screen for selective STAT3 pathway inhibitors, led to a more potent analog (11c) that demonstrated improved anti-proliferative activity against a panel of HNSCC cell lines.
Keywords:STAT3 pathway  Guanidinoquinazolines  Skraup synthesis  Structure–activity relationships  Cancer cell line screening
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