Department of Chemistry, Osmania University, Hyderabad, 500007, India.
Department of Chemistry, Osmania University, Hyderabad, 500007, India.
Eur J Med Chem. 2018 Aug 5;156:43-52. doi: 10.1016/j.ejmech.2018.06.055. Epub 2018 Jun 27.
A series of hybrid aza heterocycles containing pyrazolo[3,4-d]pyrimidin-4(5H)-ones tethered to 1,2,3-triazole 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 5l were more effective in binding with TGFBR2 than other compounds.
一系列含吡唑并[3,4-d]嘧啶-4(5H)-酮的杂氮杂环通过 1,3-偶极环加成反应合成，该反应以基于吡唑嘧啶酮的炔烃与叠氮化物为底物，以 Cu(II)催化剂为催化剂，在抗坏血酸钠存在下进行，并用其对 C6 大鼠和 U87 人神经胶质瘤细胞系进行了体外抗癌活性评估。这些化合物诱导了对 C6 大鼠和 U87 人神经胶质瘤细胞增殖的浓度依赖性抑制。化合物 5f 将细胞阻滞在细胞周期的 S 期，并在 U87 GBM 细胞系中诱导细胞凋亡。进一步的研究表明，细胞凋亡与 Caspase-3、PARP 的切割和 p53 的上调有关。基于计算机的对接研究表明，化合物 5a、5f 和 5l 与 TGFBR2 的结合比其他化合物更有效。
