title: Syntheses and biological evaluation of 1,2,3-triazole and 1,3,4-oxadiazole derivatives of imatinib.
abstract: Three novel series of 1,2,3-triazole and 1,3,4-oxadiazole derivatives of imatinib were prepared and evaluated in vitro for their cytostatic effects against a human chronic myeloid leukemia (K562), acute myeloid leukemia (HL60), and human leukemia stem-like cell line (KG1a). The structure-activity relationship was analyzed by determining the inhibitory rate of each imatinib analog. Benzene and piperazine rings were necessary groups in these compounds for maintaining inhibitory activities against the K562 and HL60 cell lines. Introducing a trifluoromethyl group significantly enhanced the potency of the compounds against these two cell lines. Surprisingly, some compounds showed significant inhibitory activities against KG1a cells without inhibiting common leukemia cell lines (K562 and HL60). These findings suggest that these compounds are able to inhibit leukemia stem-like cells.
authors: The State Key Laboratory of Elemento-Organic Chemistry, College of Pharmacy, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, PR China; High-throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of BioMedicine, Tianjin 300457, PR China.
authors: Yong-Tao
authors: YT
authors: Li
authors: The State Key Laboratory of Elemento-Organic Chemistry, College of Pharmacy, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, PR China; High-throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of BioMedicine, Tianjin 300457, PR China.
authors: Jing-Han
authors: JH
authors: Wang
authors: The State Key Laboratory of Elemento-Organic Chemistry, College of Pharmacy, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, PR China; High-throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of BioMedicine, Tianjin 300457, PR China.
authors: Cheng-Wen
authors: CW
authors: Pan
authors: The State Key Laboratory of Elemento-Organic Chemistry, College of Pharmacy, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, PR China; High-throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of BioMedicine, Tianjin 300457, PR China.
authors: Fan-Fei
authors: FF
authors: Meng
authors: High-throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of BioMedicine, Tianjin 300457, PR China.
authors: Xiao-Qian
authors: XQ
authors: Chu
authors: The State Key Laboratory of Elemento-Organic Chemistry, College of Pharmacy, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, PR China.
authors: Ya-hui
authors: YH
authors: Ding
authors: The State Key Laboratory of Elemento-Organic Chemistry, College of Pharmacy, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, PR China; High-throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of BioMedicine, Tianjin 300457, PR China.
authors: Wen-Zheng
authors: WZ
authors: Qu
authors: High-throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of BioMedicine, Tianjin 300457, PR China.
authors: Hui-ying
authors: HY
authors: Li
authors: The State Key Laboratory of Elemento-Organic Chemistry, College of Pharmacy, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, PR China; High-throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of BioMedicine, Tianjin 300457, PR China.
authors: Cheng
authors: C
authors: Yang
authors: The State Key Laboratory of Elemento-Organic Chemistry, College of Pharmacy, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, PR China.
authors: Quan
authors: Q
authors: Zhang
authors: High-throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of BioMedicine, Tianjin 300457, PR China. Electronic address: baicuigai@tjab.org.
authors: Cui-Gai
authors: CG
authors: Bai
authors: The State Key Laboratory of Elemento-Organic Chemistry, College of Pharmacy, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, PR China. Electronic address: yuechen@nankai.edu.cn.
authors: Yue
authors: Y
authors: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D000068877:Imatinib Mesylate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020014:K562 Cells; D015394:Molecular Structure; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D010069:Oxadiazoles; D014230:Triazoles; C583463:1,3,4-oxadiazole; D000068877:Imatinib Mesylate
keywords: Chronic myelogenous leukemia; Imatinib; K562; KG-1a; Synthesis