Abstract
Tumor blood vessels are an important emerging target for anti-cancer therapy. The antimitotic agent combretastatin A-4 (CA- 4), a cis-stilbene natural product isolated from the South African tree Combretum caffrum Kuntze, is the lead compound of a new class of anti-cancer drugs that target tumor vasculature. CA-4 inhibits tubulin polymerization by interacting at the colchicine binding site on tubulin. This alters the morphology of endothelial cells and causes vascular shutdown and regression of tumor vasculature.
Some tubulin-binding vascular-disrupting agents (VDAs) are currently in clinical trials for cancer therapy. As a consequence of the potential favorable applications of these compounds, several analogs projected to induce rapid and selective vascular shutdown in tumors have been synthesized during the last few years. Many of these molecules have already been tested for their effects on tubulin polymerization as well as for their antiproliferative activity and other biological properties, and possible mechanisms of action have been investigated.
The aim of the present review is to offer an overview of most recently developed combretastatin derivatives, focusing on biological effects exerted by these compounds. The published data about new analogs are presented and compared, and a detailed investigation of structure-activity relationships is described.
Keywords: Combretastatin A-4, combretastatin analogs, vascular disrupting agents, tubulin, structure-activity relationships, Tumor blood vessels, anti-cancer therapy, cis-stilbene, Combretum caffrum Kuntze, VDAs
Current Medicinal Chemistry
Title: Biological Potential and Structure-Activity Relationships of Most Recently Developed Vascular Disrupting Agents: An Overview of New Derivatives of Natural Combretastatin A-4
Volume: 18 Issue: 20
Author(s): M. Marrelli, F. Conforti, G. A. Statti, X. Cachet, S. Michel, F. Tillequin and F. Menichini
Affiliation:
Keywords: Combretastatin A-4, combretastatin analogs, vascular disrupting agents, tubulin, structure-activity relationships, Tumor blood vessels, anti-cancer therapy, cis-stilbene, Combretum caffrum Kuntze, VDAs
Abstract: Tumor blood vessels are an important emerging target for anti-cancer therapy. The antimitotic agent combretastatin A-4 (CA- 4), a cis-stilbene natural product isolated from the South African tree Combretum caffrum Kuntze, is the lead compound of a new class of anti-cancer drugs that target tumor vasculature. CA-4 inhibits tubulin polymerization by interacting at the colchicine binding site on tubulin. This alters the morphology of endothelial cells and causes vascular shutdown and regression of tumor vasculature.
Some tubulin-binding vascular-disrupting agents (VDAs) are currently in clinical trials for cancer therapy. As a consequence of the potential favorable applications of these compounds, several analogs projected to induce rapid and selective vascular shutdown in tumors have been synthesized during the last few years. Many of these molecules have already been tested for their effects on tubulin polymerization as well as for their antiproliferative activity and other biological properties, and possible mechanisms of action have been investigated.
The aim of the present review is to offer an overview of most recently developed combretastatin derivatives, focusing on biological effects exerted by these compounds. The published data about new analogs are presented and compared, and a detailed investigation of structure-activity relationships is described.
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Cite this article as:
Marrelli M., Conforti F., A. Statti G., Cachet X., Michel S., Tillequin F. and Menichini F., Biological Potential and Structure-Activity Relationships of Most Recently Developed Vascular Disrupting Agents: An Overview of New Derivatives of Natural Combretastatin A-4, Current Medicinal Chemistry 2011; 18 (20) . https://dx.doi.org/10.2174/092986711796391642
DOI https://dx.doi.org/10.2174/092986711796391642 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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