Fourteen derivatives of the marine-derived fradcarbazole A were synthesized from staurosporine. Their structures were identified by NMR and high-resolution electrospray ionization mass spectrometry (HRESIMS). The derivatives were screened in vitro for antiproliferative activity against three human leukemic cell lines (MV4-11, HL-60, K562). All of the derivatives displayed cytotoxicity against the human FLT-3 internal tandem duplication (ITD) mutant acute myeloid leukemia (AML) cell line MV4-11 with IC values of 0.32-0.96 μM. The mechanism of action studies indicated that the most effective 3-chloro-5‴-fluorofradcarbazole A () induced apoptosis of the MV4-11 cells and arrested the cell cycle at the G/G phase. Furthermore, compound can reduce the expression of FLT-3, CDK2, and c-kit. The results suggest that 3-chloro-5‴-fluorofradcarbazole A () is a potential candidate for developing novel anti-AML agents in the future.
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