Anticancer activity, toxicity and pharmacokinetic profile of an indanone derivative

被引：45

作者：

Chanda, Debabrata ^{[1
]}

Bhushan, Shashi ^{[2
]}

Guru, Santosh K. ^{[2
]}

Shanker, Karuna ^{[1
]}

Wani, Z. A. ^{[2
]}

Rah, B. A. ^{[2
]}

Luqman, Suaib ^{[1
]}

Mondhe, Dilip M. ^{[2
]}

Pal, Anirban ^{[1
]}

Negi, Arvind S. ^{[1
]}

机构：

[1] Cent Inst Med & Aromat Plants CSIR CIMAP, Lucknow 226015, Uttar Pradesh, India

[2] Indian Inst Integrat Med CSIR IIIM, Canc Pharmacol Div, Jammu 180001, India

来源：

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES | 2012年 / 47卷 / 05期

关键词：

Gallic acid; Indanone; In vivo anticancer activity; Tubulin polymerisation inhibition; Acute oral toxicity; Pharmacokinetics; SAFETY EVALUATION; NATURAL-PRODUCTS; VEGF EXPRESSION; CANCER; APOPTOSIS; AGENTS; CELLS; PATHWAYS; RATS;

D O I：

10.1016/j.ejps.2012.08.013

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The present study describes anticancer effect of gallic acid based indanone derivative (1). Indanone 1 exhibited in vivo anticancer activity against Erhlich ascites carcinoma in Swiss albino mice by inhibiting tumor growth by 54.3% at 50 mg/kg b.wt. It showed antitubulin effect by inhibiting tubulin polymerase enzyme. In cell cycle analysis, it inhibited G2/M phase and induced apoptosis. It significantly suppressed VEGF-R1, VEGF-R2 and HIF-alpha in human breast cancer MCF-7 cells, thus exhibiting antiangiogenic activity. In acute oral toxicity, indanone 1 was well tolerated and was found to be non-toxic up to 1000 mg/kg b.wt. in Swiss albino mice. Pharmacokinetic studies in rabbits revealed rate of absorption, half life, volume of distribution with high plasma and blood clearance after iv. administration. Indanone 1, is a safe and moderately active anticancer agent. (C) 2012 Elsevier B.V. All rights reserved.

引用

页码：988 / 995

页数：8

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