title: Design, synthesis, and evaluation of curcumin-derived arylheptanoids for glioblastoma and neuroblastoma cytotoxicity.
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.
authors.affiliation: Department of Chemistry and Biochemistry, Mike and Josie Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, United States.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Campos
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Gianino
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Bailey
authors.forename: Mary E
authors.initials: ME
authors.lastname: Baluyut
authors.forename: Constanze
authors.initials: C
authors.lastname: Wiek
authors.forename: Helmut
authors.initials: H
authors.lastname: Hanenberg
authors.forename: Harlan E
authors.initials: HE
authors.lastname: Shannon
authors.forename: Karen E
authors.initials: KE
authors.lastname: Pollok
authors.forename: Brandon L
authors.initials: BL
authors.lastname: Ashfeld
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003474:Curcumin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000633:toxicity; D015195:Drug Design; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D003474:Curcumin
keywords: Arylheptanoids; Curcumin; Glioblastoma; Neuroblastoma; Relay catalysis