Synthesis of pyrazolo[3,4-d]pyrimidin-4(5H)-ones tethered to 1,2,3-triazoles and their evaluation as potential anticancer agents
Synthesis of pyrazolo[3,4-d]pyrimidin-4(5H)-ones tethered to 1,2,3-triazoles and their evaluation as potential anticancer agents
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DOI：
10.1016/j.ejmech.2018.06.055
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发表时间：
2018-08-05
影响因子：
6.7
通讯作者：
Babu, Phanithi Prakash
中科院分区：
文献类型：
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作者：
Allam, Muralidhar;Bhavani, A. K. D.;Babu, Phanithi Prakash
在抗坏血酸钠存在下，以1，3-偶极环加成反应合成了1，3-吡唑并嘧啶-4(5H)-吡唑并[3，4-d]嘧啶-4(5H)杂化杂环化合物。这些化合物对C6大鼠和U87人脑胶质瘤细胞的增殖具有浓度依赖性的抑制作用。化合物5f使U87GBM细胞停滞于S期，并诱导其发生凋亡。此外，Caspase-3、PARP的裂解和P53的上调也证明了细胞的凋亡。在电子对接中的研究表明，化合物5a、5f和51与TGFBR2的结合比其他化合物更有效。(C)2018年爱思唯尔·马森SAS。版权所有。
A series of hybrid aza heterocycles containing pyrazolo[3,4-d]pyrimidin-4(5H)-ones tethered to 1,2,3triazole scaffold were synthesized from 1,3-dipolar cycloaddition reaction of pyrazolopyrimidinone based alkyne with azides using Cu(II) catalyst in presence of sodium ascorbate and evaluated for their anticancer efficacy in vitro against C6 rat and U87 human glioma cell lines. These compounds induced a concentration dependent inhibition of C6 rat and U87 human glioma cell proliferation. Compound 5f arrested the cells at S-phase of the cell cycle and induced apoptosis in U87 GBM cell lines. Further, apoptosis was evidenced by the cleavage of Caspase-3, PARP and up regulation of p53. In silico docking studies reveal that the compounds 5a, 5f and 51 were more effective in binding with TGFBR2 than other compounds. (C) 2018 Elsevier Masson SAS. All rights reserved.