Synthesis and Molecular Docking of Some Grossgemin Amino Derivatives as Tubulin Inhibitors Targeting Colchicine Binding Site

Abstract

Six amino derivatives of grossgemin (2–7) were synthesized according to the reported essential pharmacophoric features of colchicine binding site inhibitors (CBSIs). The derivatives 4–6 were obtained for the first time. The pharmacophoric features of 2–7 as CBSIs were studied to be almost identical. Furthermore, the 3D-flexible alignment of compound 5 as a representative example with colchicine showed a very good overlapping. In agreement, compounds 2–7 docked into CBS with binding modes very similar to that of colchicine and exhibited binding free energies of −24.57, −25.05, −32.16, −29.34, −26.38, and −26.86 (kcal/mol), respectively. The binding free energies of 4–7 were better than that of colchicine (−26.13 kcal/mol) with a noticeable superiority to compound 4.