Discovery of A Novel Synthetic Thiazole-benzimidazole Conjugate that Acts as a Potent Pancreatic Lipase Inhibitor using in silico and in vitro Approaches
Amr Salah Abouzied, Mohammed Khaled Bin Break, Bader Huwaimel, Weiam Hussein, Ahmed D. Alafnan, Kareem M. Younes · Indian Journal of Pharmaceutical Education and Research · 2023
Aim/ Background: Pancreatic lipase (PL) inhibition has been suggested to be an effective method for obesity management.In this study, 10 novel thiazole-benzimidazole conjugates were designed.Materials and Methods: Conjugates were initially screened via in silico experiments, such as ADMET analysis and molecular docking, to identify the most promising PL inhibitors.Results: Results revealed that compounds 3, 6 and 8 had the most optimum druglikeness properties, and the highest binding affinity to PL, with binding energies of -7.7, -7.5 and -8.1 kcal/mol, respectively.Therefore, these promising derivatives were then synthesized and subjected to an in PL inhibition assay to validate the results of the in silico experiments.The synthetic compounds were fully characterized via FTIR, 1 H-NMR, 13 C-NMR and LCMS.Results of the enzymatic assay revealed that 3, 6 and 8 inhibited PL potently with high inhibition rates of greater than 80% at the highest tested dose, and demonstrated IC 50 values of 68.53, 54.97 and 50.09μM, respectively.Compound 8 was the most active derivative and displayed comparable activity to orlistat which possessed an IC 50 value of 39.18μM.Conclusion: Therefore, we report the discovery of compound 8 as a highly potent PL inhibitor that could act as a lead compound to develop novel anti-obesity agents.