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.