Molecular modelling studies on Arylthioindoles as potent inhibitors of tubulin polymerization

The crucial role played by microtubules in the life of eukaryotic cell makes tubulin an important route for the anticancer therapy. The Arylthioindoles (ATIs) along with the corresponding ketone and methylene compounds are potent tubulin assembly inhibitors. We are here reporting the result of a series of docking and molecular dynamics experiments on this series of compounds. The results obtained from our in silico studies not only provided us with an insight on the nature of the binding of the ATIs to tubulin, but were also at the core of the design of a new series of potent inhibitors of tubulin polymerization.

Graphical abstractMolecular modelling studies on the binding of Arylthioindoles to tubulin colchicine site.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Molecular docking and dynamics simulations. ► Poor correlation between docking score and biological activity. ► Good correlation between dynamics score and biological activity. ► Overcame the metabolic instability of analyzed compounds. ► Design of new compounds