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

<b>Aim:</b> A series of benzimidazole-acrylonitrile derivatives <b>TM1-TM53</b> were designed with urease inhibition approach.<b>Materials & methods:</b> <b>TM1-TM53</b> 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.<b>Results:</b> 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 <b>TM11</b>, clarified its mode of action as a mixed inhibitor. A molecular docking study on <b>TM6</b>, <b>TM11</b> and <b>TM21</b>, was performed and the results showed the main residues inside the active site of the enzyme. All <b>TM1-TM53</b> were also studied <i>in silico</i> 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 <b>TM1-TM53</b> as a fungicides.<b>Conclusion:</b> 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.