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

R. I. Jalmakhanbetova, Eslam B. Elkaeed, Ibrahim H. Eissa, Ahmed M. Metwaly, Ye. M. Suleimen
2021 Journal of Chemistry  
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
more » ... milar 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.
doi:10.1155/2021/5586515 doaj:f2099d5ee8ba42a0a2b49f69378250d2 fatcat:v6poxcb3jbasrfgyqqk2qnwgue