Syntheses and biological evaluation of 1,2,3-triazole and 1,3,4-oxadiazole derivatives of imatinib

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• 作者：Yong-Tao Li^a ; ^b ; ^&dagger ; ; Jing-Han Wang^a ; ^b ; ^&dagger ; ; Cheng-Wen Pan^a ; ^b ; Fan-Fei Meng^a ; ^b ; Xiao-Qian Chu^b ; Ya-hui Ding^a ; Wen-Zheng Qu^a ; ^b ; Hui-ying Li^b ; Cheng Yang^a ; ^b ; Quan Zhang^a ; Cui-Gai Bai^b ; ^{baicuigai@tjab.org" class="auth_mail" title="E-mail the corresponding author} ; Yue Chen^a ; ^{yuechen@nankai.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Chronic myelogenous leukemia ; K562 ; KG-1a ; Imatinib ; Synthesis
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 March 2016
• 年：2016
• 卷：26
• 期：5
• 页码：1419-1427
• 全文大小：3151 K

文摘

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.