title: Synthesis and anti-acute myeloid leukemia activity of C-14 modified parthenolide derivatives.
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 IC50values 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.
authors.affiliation: 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.
authors.forename: Zhongjin
authors.initials: Z
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Beijia
authors.initials: B
authors.lastname: Kuang
authors.affiliation: 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.
authors.forename: Ning
authors.initials: N
authors.lastname: Kang
authors.affiliation: 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.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Ding
authors.affiliation: 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.
authors.forename: Weizhi
authors.initials: W
authors.lastname: Ge
authors.affiliation: 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.
authors.forename: Lihui
authors.initials: L
authors.lastname: Lian
authors.affiliation: 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.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: 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.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Wei
authors.affiliation: 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. Electronic address: yuechen@nankai.edu.cn.
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 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. Electronic address: zhangquan612@163.com.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D012717:Sesquiterpenes; C002669:parthenolide
keywords: Acute myeloid leukemia; Apoptosis; KG1a; Parthenolide; Synthesis