Synthesis of methoxy- and bromo-substituted indirubins and their activities on apoptosis induction in human neuroblastoma cells.

This paper reports the synthesis of methoxy- and bromo-indirubins, and their antiproliferative activities in human neuroblastoma. Among 20 compounds, 5'-methoxyindirubin induced cell death in human neuroblastoma cells (IMR-32, SK-N-SH and NB-39) without inhibiting normal cells (NHDF and HUVEC). Typical morphologic features of apoptosis were observed in 5'-methoxyindirubin-treated cells by Hoechst 33342 staining. Additional studies by flow cytometry support apoptosis induction. These data suggest that 5'-methoxyindirubin might be an effective drug for treatment of neuroblastoma.