Synthesis of pyrazolo[3,4-d]pyrimidin-4(5H)-ones tethered to 1,2,3-triazoles and their evaluation as potential anticancer agents

被引：60

作者：

Allam, Muralidhar ^{[1
]}

Bhavani, A. K. D. ^{[1
]}

Mudiraj, Anwita ^{[2
]}

Ranjan, Nikhil ^{[2
]}

Thippana, Mallikarjuna ^{[2
]}

Babu, Phanithi Prakash ^{[2
]}

机构：

[1] Osmania Univ, Dept Chem, Hyderabad 500007, Andhra Pradesh, India

[2] Univ Hyderabad, Sch Life Sci, Dept Biotechnol & Bioinformat, Hyderabad 500046, Telangana, India

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2018年 / 156卷

关键词：

Pyrazolo[3,4-d]pyrimidin-4(5H)-one; 1,2,3-Triazole; Glioma; Anti-cancer activity; Apoptosis; TGF-BETA; CELL-DEATH; DERIVATIVES; APOPTOSIS; ANTIBACTERIAL; INHIBITORS; DOCKING; DESIGN;

D O I：

10.1016/j.ejmech.2018.06.055

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：43 / 52

页数：10

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