C-14 修饰的紫菀酮衍生物的合成及抗急性髓系白血病活性。
Synthesis and anti-acute myeloid leukemia activity of C-14 modified parthenolide derivatives.
机构信息
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, People's Republic of China.
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, People's Republic of China.
出版信息
Eur J Med Chem. 2017 Feb 15;127:296-304. doi: 10.1016/j.ejmech.2016.12.044. Epub 2016 Dec 23.
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 IC 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 (IC = 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.
小白菊内酯（PTL）选择性地消除白血病干细胞（LSCs）。合成了一系列在 PTL 的 C-14 上进行修饰的 PTL 衍生物，其中大多数衍生物对 HL-60 和 KG1a 具有高活性。最有效的化合物 6j 对 KG1a 和 HL-60 的 IC 值分别为 0.4 μM 和 1.1 μM，分别比 PTL 高 8.7 倍和 3.8 倍。此外，与高抗 AML 活性相比，化合物 6j 对正常细胞的毒性相对较低（IC = 12.3 μM）。AML 细胞 KG1a 和 HL-60 的选择性指数分别为 30.8 和 11.2。初步研究表明，化合物 6j 可诱导 KG1a 细胞凋亡。
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