Design of Combretastatin A-4 Analogs as Tubulin Targeted Vascular Disrupting Agent with Special Emphasis on Their Cis-Restricted Isomers

Author(s): Harish Rajak, Pramod Kumar Dewangan, Vijay Patel, Deepak Kumar Jain, Avineesh Singh, Ravichandran Veerasamy, Prabodh Chander Sharma, Anshuman Dixit.

Journal Name: Current Pharmaceutical Design

Volume 19 , Issue 10 , 2013

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Abstract:

Tubulin protein is a highly imperative and feasible goal for anticancer drug discovery. Hundreds of naturally occurring, semi synthetic and synthetic antitubulin agents have been reported till now. Among these, Combretastatin A - 4 (CA - 4) is effective antimitotic agent possessing potent cytotoxicity against a panel of cancer cells, including multi-drug resistant cancer cell lines. The inadequate water solubility and inactivation of these analogs during storage limit their use as clinical anticancer agents. To overcome these shortcomings, numerous water soluble amino analogs, amino acid derivative, phosphate prodrug (CA - 4P) and cis-locked CA - 4 have been developed with distinctive attributes of antitubulin and antivascular properties in a wide variety of preclinical tumor models. Subsequently, several heterocycle based cis restricted CA - 4 analogs are being reported for antitumor activity against collection of cancer cell lines. This review recapitulates the rational design, structure activity relationship, pharmacokinetic and pharmacodynamic profile of synthesized cis restricted CA - 4 analogs.

Keywords: CA - 4, antitubulin, antivascular, cytotoxicity, structure-activity relationship, antimitotic agents, Combretum caffrum, anticancer

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Article Details

VOLUME: 19
ISSUE: 10
Year: 2013
Page: [1923 - 1955]
Pages: 33
DOI: 10.2174/1381612811319100013
Price: $65

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