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<sub>50</sub> values of 0.32-0.96 μM. The mechanism of action studies indicated that the most effective 3-chloro-5‴-fluorofradcarbazole A (<b>6</b>) induced apoptosis of the MV4-11 cells and arrested the cell cycle at the G<sub>0</sub>/G<sub>1</sub> phase. Furthermore, compound <b>6</b> can reduce the expression of FLT-3, CDK2, and c-kit. The results suggest that 3-chloro-5‴-fluorofradcarbazole A (<b>6</b>) is a potential candidate for developing novel anti-AML agents in the future.