Synthesis and anticancer activity of novel spiro-isoxazoline and spiro-isoxazolidine derivatives of α-santonin

被引：78

作者：

Khazir, Jabeena ^{[2
]}

Singh, Parvinder Pal ^{[2
]}

Reddy, D. Mahendhar ^{[1
]}

Hyder, Irfan ^{[1
]}

Shafi, Syed ^{[3
]}

Sawant, S. D. ^{[2
]}

Chashoo, Gousia ^{[2
]}

Mahajan, Ajay ^{[2
]}

Alam, M. S. ^{[3
]}

Saxena, A. K. ^{[2
]}

Arvinda, S. ^{[2
]}

Gupta, B. D. ^{[2
]}

Kumar, H. M. Sampath ^{[1
]}

机构：

[1] Indian Inst Chem Technol, NPC Div, Hyderabad 500007, Andhra Pradesh, India

[2] Indian Inst Integrat Med, Div Med Chem, Jammu 180001, India

[3] Jamia Hamdard, Dept Chem, New Delhi 110062, India

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 63卷

关键词：

alpha-Santonin; Spiro-derivatives; Anticancer; NF-kappa B (p65) inhibitors; NF-KAPPA-B; NATURAL-PRODUCTS; STEM-CELLS;

D O I：

10.1016/j.ejmech.2013.01.003

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In the present study, novel Spiro derivatives of alpha-santonin were prepared and tested for their anticancer activity against a panel of six human cancer cell lines. Spiro-isoxazoline and spiro-isoxazolidine derivatives have been generated on C-ring of alpha-santonin (alpha-methylene-gamma-butyrolactone) by the 1,3-dipolar cycloaddition of alpha-santonin derivative 6 with nitrile oxides 7 and nitrones 9 respectively. Among all, compound 10b '' had shown IC50 of 0.01, 0.5 and 0.3 mu M against PC-3, THP-1 and MCF-7 cell lines respectively. Further, flow cytometry studies showed that PC-3 cells treated with the spiro-isoxazolidine derivative 10b '' were arrested in the sub G1 phase of the cell cycle in a concentration dependent manner. The spiro-isoxazolidine derivative 10b '' also showed concentration dependent inhibitory activity against NF-kappa B, p65 with 57% inhibition in 24 h at 10 mu M. (C) 2013 Elsevier Masson SAS. All rights reserved.

引用

页码：279 / 289

页数：11

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