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Imidazo[4,5-b]pyridine Derived Tubulin Polymerization Inhibitors

In the development of novel antitumor drugs considerable interest is focused on the development, design and biological activity of novel heteroaromatic systems as potential tubulin polymerization inhibitors. Microtubules, which are formed through the polymerization of heterodimers, have an important role in cellular shape organization, cell division, mitosis and intracellular movement and thus are a key dynamic structural components in cells. Since imidazo[4, 5-b]pyridine derivatives, as one of the privileged medicinal scaffolds, have not been fully explored as tubulin polymerization inhibitors, we have designed novel imidazo[4, 5-b]pyridine derived acrylonitriles, described their synthesis and structural characterization. (Scheme 1) Antiproliferative activity was tested in vitro against nine human cancer cells in order to study the influence of the substituents placed at the phenyl ring and at the N-atom of the imidazo[4, 5-b]pyridine nuclei.1 Both experimental and computational methods confirmed the same biological target. Combination of docking and molecular dynamic simulation further explained interaction with biological target.

imidazo[4, 5-b]pyridine ; synthesis ; biological activity ; computational chemistry

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