Delineation of Current Development of Antimitotic Compounds Targeting Cytoskeletal Protein Tubulin and Microtubule in the Cancer Therapy

Author(s): Suvroma Gupta .

Journal Name: Current Chemical Biology

Volume 8 , Issue 3 , 2014

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Abstract:

Tubulin-Microtubule (MT) system has long been implicated in multiple crucial cellular functions like cell division, maintenance of cell shape and structure, intracellular transport and propagation of signal transduction. This complex entity composed of αβ tubulin heterodimer can account for mitotic arrest followed by induction of cell suicide event due to its dynamic character. Being a target for a number of natural as well as synthetic small molecules blocking cell cycle progression has made tubulin-MT system an effective subject of research. This drive to combat proliferation of cancerous cell growth is still continuing with the advent of small molecule inhibitors. These antitubulin agents can be divided into two flavors; promoting assembly of tubulin to stable MT and inhibiting polymerization of αβ tubulin to MT polymer. But in most of the cases an additional subtle mechanism known as microtubule dynamics (catastrophe or treadmilling and rescue) has been attenuated by small molecule inhibitors imposing an impasse to the progress of cell cycle. Colchicine is the ancient antitubulin drug inhibiting polymerization but cannot be utilized with full potential due to its necrotoxic behavior. That is why colchicine site inhibitors (CSI) have been designed, synthesized and tested in order to get potential antimitotic agents of future promise. In this review, an effort has been initiated to unravel the mechanistic approach using MTs as anticancer drug target focusing colchicine binding site. Along with the history of development of CSIs, a modern update of recently explored colchicine site targeting agents has been discussed with a prelude of MT dynamics, role of microtubule associated proteins (MAPs) affecting MT stability and with a vivid description of factors conferring resistance to antimitotic agents.

Keywords: Apoptosis, colchicine, dynamics, microtubule.

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Article Details

VOLUME: 8
ISSUE: 3
Year: 2014
Page: [165 - 183]
Pages: 19
DOI: 10.2174/221279680803150420094816
Price: $58

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