Title:New Ligands of the Tubulin Colchicine Site Based on X-Ray Structures
Volume: 14
Issue: 20
Author(s): Raquel Alvarez, Manuel Medarde and Rafael Pelaez
Affiliation:
Keywords:
Antimitotic, cancer, colchicine site ligands, microtubules, molecular docking, structure-based drug design, tubulin,
X-ray structures.
Abstract: Colchicine site ligands have proved to be potent inhibitors of tubulin polymerization, which
leads them not only to display cytotoxic effects but also vascular disrupting effects on tumour neovasculature.
In recent years, many compounds have been designed, synthesized and evaluated in order to improve
the potency, stability and physicochemical properties of these agents with the aim of developing an agent
that could reach the clinical assay level. Here we analyze the eleven X-ray structures of tubulin in complex with ligands at
the colchicine site by dividing it into four different zones of interaction, we review the new compounds that have appeared
in the literature since 2008 and that were designed based on any of these X-ray structures and, finally, we describe our latest
results in the design of new potent antimitotic indole derivatives that have confirmed the flexibility of one of the zones
described for the colchicine site.
