Design, synthesis, and evaluation of curcumin-derived arylheptanoids for glioblastoma and neuroblastoma cytotoxicity
2013
Campos, Catherine A. | Gianino, Joseph B. | Bailey, Barbara J. | Baluyut, Mary E. | Wiek, Constanze | Hanenberg, Helmut | Shannon, Harlan E. | Pollok, Karen E. | Ashfeld, Brandon L.
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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