Anticancer activity of dihydropyrazolo[1,5-c]quinazolines against rat C6 glioma cells via inhibition of topoisomerase II

被引：16

作者：

Kaur, Gagandeep ^{[1
]}

Cholia, Ravi P. ^{[2
]}

Joshi, Gaurav ^{[1
]}

Amrutkar, Suyog M. ^{[3
]}

Kalra, Sourav ^{[4
]}

Mantha, Anil K. ^{[2
]}

Banerjee, Uttam C. ^{[3
]}

Kumar, Raj ^{[1
]}

机构：

[1] Cent Univ Punjab, Dept Pharmaceut Sci & Nat Prod, Lab Drug Design & Synth, Bathinda 151001, India

[2] Cent Univ Punjab, Dept Anim Sci, Bathinda, India

[3] NIPER, Dept Pharmaceut Technol Biotechnol, Mohali, India

[4] Cent Univ Punjab, Dept Human Genet & Mol Med, Bathinda, India

来源：

ARCHIV DER PHARMAZIE | 2018年 / 351卷 / 06期

关键词：

cancer; cell cycle; dihydropyrazolo[1; 5-c]quinazoline; rat C6 glioma cells; topoisomerases; GROWTH-FACTOR RECEPTOR; DNA TOPOISOMERASES; ALPHA; EXPRESSION; MECHANISM; DISCOVERY; DESIGN;

D O I：

10.1002/ardp.201800023

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The design and synthesis of dihydropyrazolo[1,5-c]quinazolines (1a-h) as human topoisomerase II (TopoII) catalytic inhibitors are reported. The compounds were investigated for their antiproliferative activity against the C6 rat glial cell line. Two compounds, 1b and 1h, were found to be potent cytotoxic agents against glioma cells and exerted selective TopoII inhibitory activity. Furthermore, the compounds induced alterations in reactive oxygen species levels as measured by DCFDA assay and were found to induce cell cycle arrest at the G1 phase at lower concentrations and profound apoptosis at higher concentrations. The interaction of selected investigational molecules with TopoII was further corroborated by molecular modeling.

引用

页数：11

共 34 条

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