Molecular Modelling of Mebendazole Polymorphs as a Potential Colchicine Binding Site Inhibitor

Preclinical and clinical studies on Mebendazole revealed its potential as anticancer agent. We therefore aimed to investigate its binding interactions with one of the most important cancer targets (Tubulin protein) depending on its structural similarity with the original co-crystallized ligand (Nocodazole), besides characterization of electronic configuration at molecular level. By reviewing binding mode and hydrogen bonds length between the three polymorphs of Mebendazole (MBZ) and colchicine binding site on tubulin protein, form B of MBZ is the form expected to bind more efficiently with tubulin protein among other forms. The calculated physicochemical properties revealed also that form B is the most lipophilic form, hence, can more flawlessly cross blood brain barrier in order to target brain tumors. Our study has ramifications to consider form B of MBZ in the clinical trials of repurposing MBZ in oncology, because only forms A and C have been considered while form B was abandoned.