Synthesis and anti-acute myeloid leukemia activity of C-14 modified parthenolide derivatives.
Basic Information
ID: ALA3997783
Journal: Eur J Med Chem
Title: Synthesis and anti-acute myeloid leukemia activity of C-14 modified parthenolide derivatives.
Authors: Yang Z, Kuang B, Kang N, Ding Y, Ge W, Lian L, Gao Y, Wei Y, Chen Y, Zhang Q.
Abstract: Parthenolide (PTL) selectively ablates leukemia stem cells (LSCs). A series of PTL derivatives with modifications on C-14 of PTL was synthesized, and most of the derivatives showed high activities against HL-60 and KG1a. The most potent compound 6j exhibited IC50 values of 0.4 μM and 1.1 μM against KG1a and HL-60, respectively, which were 8.7 and 3.8 folds more potent than those of PTL, respectively. Moreover, compound 6j showed relatively low toxicity to normal cells (IC50 = 12.3 μM) comparing with its high anti-AML activity. The selectivity indexes for AML cells KG1a and HL-60 were 30.8 and 11.2, respectively. Preliminary study revealed that compound 6j could induce apoptosis of KG1a cells.
CiteXplore: 28068601
DOI: 10.1016/j.ejmech.2016.12.044
Patent ID: ┄