Novel Benzimidazole Derivatives as Effective Inhibitors of Prolyl Oligopeptidase: Synthesis, <i>in Vitro and in Silico</i> Analysis
Abdul Shakoor, Aftab Alam, Faheem Jan, Momin Khan, Mumtaz Ali, Naeem Ullah, Ajmal Khan, Abdullah F. Alasmari, Fawaz Alasmari, Ahmed Al‐Ghafri, Ahmed Al‐Harrasi
Abstract
Background: This research aims to discover novel derivatives having potential therapeutic applications in treating conditions related to prolyl oligopeptidase (POP) dysfunction. Method: Novel benzimidazole derivatives have been synthesized, characterized and screened for their in vitro POP inhibition. Results: All these derivatives showed excellent-to-good inhibitory activities in the range of IC50 values of 3.61 ± 0.15 to 43.72 ± 1.18 μM, when compared with standard Z-prolyl-prolinal. The docking analysis revealed the strong interactions between our compounds and the target enzyme, providing critical insights into their binding affinities and potential implications for drug development. Conclusion: The significance of these compounds in targeting POP enzyme offers promising prospects for future research in the field of neuropharmacology.