Synthesis and evaluation of hybrid molecules targeting the vinca domain of tubulin.

Abstract

Some hybrids of vinca alkaloids and phomopsin A, linked by a glycine pattern, have been synthesized in one or two steps, by an insertion reaction and shown to inhibit microtubule assembly. These compounds have been elaborated in order to interact with both the "vinca site" and the "peptide site" of the vinca domain in tubulin. Two out of three hybrids are potent inhibitors of microtubules assembly and they present good cytotoxicity against different cell lines. Molecular modelling studies show that they could bind, within the vinca domain, in similar spatial regions as those of vinca and phomopsin thanks to the flexibility provided by the glycine linker used to elaborate these hybrids.

DOI: 10.1039/c4ob02114b

Cite this paper

@article{Gherbovet2015SynthesisAE, title={Synthesis and evaluation of hybrid molecules targeting the vinca domain of tubulin.}, author={Olga Gherbovet and Pedro A. S{\'a}nchez-Murcia and Mar{\'i}a Concepci{\'o}n Garc{\'i}a Alvarez and J Bignon and Sylviane Thoret and Federico Gago and Fanny Roussi}, journal={Organic & biomolecular chemistry}, year={2015}, volume={13 10}, pages={3144-54} }