Design,synthesis, and evaluation of curcumin-derived arylheptanoids for glioblastoma and neuroblastoma cytotoxicity |
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Authors: | Catherine A Campos Joseph B Gianino Barbara J Bailey Mary E Baluyut Constanze Wiek Helmut Hanenberg Harlan E Shannon Karen E Pollok Brandon L Ashfeld |
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Institution: | 1. Department of Chemistry and Biochemistry, Mike and Josie Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, United States;2. Herman B Wells Center for Pediatric Research, Department of Pediatrics, Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, United States;3. Indiana University Simon Cancer Center, Indiana University School of Medicine (IUSM), Indianapolis, IN 46202, United States;4. Department of Otorhinolaryngology (ENT), Heinrich Heine University School of Medicine, Düsseldorf 40225, Germany;5. Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, United States;6. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, United States |
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Abstract: | Using an innovative approach toward multiple carbon–carbon bond-formations that relies on the multifaceted catalytic properties of titanocene complexes we constructed a series of C1–C7 analogs of curcumin for evaluation as brain and peripheral nervous system anti-cancer agents. C2-Arylated analogs proved efficacious against neuroblastoma (SK-N-SH & SK-N-FI) and glioblastoma multiforme (U87MG) cell lines. Similar inhibitory activity was also evident in p53 knockdown U87MG GBM cells. Furthermore, lead compounds showed limited growth inhibition in vitro against normal primary human CD34+hematopoietic progenitor cells. Taken together, the present findings indicate that these curcumin analogs are viable lead compounds for the development of new central and peripheral nervous system cancer chemotherapeutics with the potential for little effects on normal hematopoietic progenitor cells. |
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Keywords: | Curcumin Relay catalysis Arylheptanoids Glioblastoma Neuroblastoma |
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