Synthesis, Fungicidal Activity, and Molecular Docking of 2-Acylamino and 2-Thioacylamino Derivatives of 1-benzo[]imidazoles as Anti-Tubulin Agents.

This work deals with the synthesis and evaluation of fungicidal activity of benzimidazole derivatives, which are structural analogues of commercial anti-tubulin fungicides. A number of -acyl and -thioacyl derivatives of 2-amino-1-benzo[]imidazole were prepared, and their fungicidal activity against 13 strains of phytopathogenic fungi was studied. The most active compounds against the majority of the studied strains were , , and , and the EC values of these compounds were in the range 2.5-20 μg/mL. Compound showed the highest activity against the strain, the growth of which is not suppressed by carbendazim. The formation of ligand-receptor complexes of various tautomeric forms of the studied benzimidazoles with homologous models of β-tubulins of , , and was modeled. Induced fit docking has been used for the simulation. The obtained data suggest the possibility of binding of benzimidazole fungicides to β-tubulin in the ″nocodazole cavity″ in the tautomeric form bearing a double exocyclic C═N bond. The importance of the formation of hydrogen bonds of benzimidazoles with the amino acid residue Val236 along with the Glu198 residue is also revealed in the present study.