In Silico Drug Design and Molecular Docking Study of Some Related Structural Isomers of Nocodazole Analogues as Tubulin-Polymerization Inhibitors

Abstract

The molecular docking simulation and ADMET prediction have been performed to calculate and predict the new available drugs as tubulin-polymerization inhibitors, focusing on the specific groups of 2-substituted benzimidazole based which are some related structural isomers of nocodazole analogues. The ADMET prediction shows that the toxicity for the structural isomers substituted at (2,7) or (2,4) positions (for Ai or Di) are significantly lower than at (2,6) or (2,5) positions (for Bi or Ci) for all substituents. The receptor-ligand interaction energies suggest that the representative compounds of A10&D10, A8&D8, and A4&D4, respectively, are the most reactive with significantly low toxicity compared to a true drug. These available drugs provide the lowest-energy conformations within colchicine-binding site that belongs to PDB code: 3E22, rather than PDB code: 5CA1, 1SA0, or 1SA1.