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Anticancer activity, toxicity and pharmacokinetic profile of an indanone derivative.

Abstract
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-α 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 i.v. administration. Indanone 1, is a safe and moderately active anticancer agent.
AuthorsDebabrata Chanda, Shashi Bhushan, Santosh K Guru, Karuna Shanker, Z A Wani, B A Rah, Suaib Luqman, Dilip M Mondhe, Anirban Pal, Arvind S Negi
JournalEuropean journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 47 Issue 5 Pg. 988-95 (Dec 18 2012) ISSN: 1879-0720 [Electronic] Netherlands
PMID23017432 (Publication Type: Journal Article)
CopyrightCopyright © 2012 Elsevier B.V. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Cyclin-Dependent Kinase Inhibitor p21
  • Indans
  • NF-kappa B
  • Tubulin Modulators
  • indacrinone
Topics
  • Animals
  • Antineoplastic Agents (pharmacokinetics, therapeutic use, toxicity)
  • Breast Neoplasms (drug therapy, metabolism)
  • Carcinoma, Ehrlich Tumor (drug therapy, pathology)
  • Cell Cycle (drug effects)
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase Inhibitor p21 (metabolism)
  • Female
  • Humans
  • Indans (pharmacokinetics, therapeutic use, toxicity)
  • Leukocytes (drug effects)
  • Male
  • Mice
  • NF-kappa B (metabolism)
  • Rabbits
  • Tubulin Modulators (pharmacokinetics, therapeutic use, toxicity)

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