Benzimidazole-acrylonitrile hybrid derivatives act as potent urease inhibitors with possible fungicidal activity

Aim: A series of benzimidazole-acrylonitrile derivatives TM1–TM53 were designed with urease inhibition approach. Materials & methods:TM1–TM53 were synthesized and characterized (¹H Nuclear Magnetic Resonance (NMR), ¹³C NMR, Mass Spectroscopy (MS) and IR) and subjected to urease inhibition assay using commercial assay kit. A molecular docking study was also performed using Autodock tool software. Results: Except six compounds, target molecules exhibited a higher urease inhibition effect (IC₅₀: 1.22–28.45 μM) than hydroxyurea (IC₅₀: 100 μM). kinetic study on TM11, clarified its mode of action as a mixed inhibitor. A molecular docking study on TM6, TM11 and TM21, was performed and the results showed the main residues inside the active site of the enzyme. All TM1–TM53 were also studied in silico using molecular docking techniques to evaluate their potential to inhibit succinate dehydrogenase in comparison to fluxapyroxad as standard. Docking study revealed the high potential of TM1–TM53 as a fungicides. Conclusion: Obtained results exhibited the high activity of benzimidazole-acrylonitrile derivatives as urease inhibitors and their possible potential as fungicide agents. So, it will be beneficial to do more bioactivity investigation on this family of compounds.