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Indian Journal of Pharmaceutical Education and ResearchNOW IN
Article

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 Abouzied1,2★, Mohammed Khaled Bin Break1, Bader Huwaimel1, Weiam Hussein1, Ahmed Alafnan3, Kareem Mahmoud Younes1,4★ Corresponding author

  1. 1Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, Hail, SAUDI ARABIA.
  2. 2Department of Pharmaceutical Chemistry, National Organization for Drug Control and Research (NODCAR), Giza, EGYPT.
  3. 3Department of Pharmacology and Toxicology, College of Pharmacy, University of Hail, Hail, SAUDI ARABIA.
  4. 4Department of Analytical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, EGYPT.

CORRESPONDENCE

Amr Salah Abouzied

University of Hail, College of Pharmacy, Department of Pharmaceutical Chemistry, Hail-682507, SAUDI ARABIA.

as.ibrahim@uoh.edu.sa

Received: 09-06-2022; Revised: 13-08-2022; Accepted: 11-10-2022.

Volume 57, Issue 1 · pp. 218–227 · PUBLISHED 2023 · DOI: 10.5530/001954642131

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ABSTRACT

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 drug likeness 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, 1H-NMR, 13C-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 IC50 values of 68.53, 54.97 and 50.09 μM, respectively. Compound 8 was the most active derivative and displayed comparable activity to orlistat which possessed an IC50 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.

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    Abouzied, A. S., Break, M. K. B., Huwaimel, B., Hussein, W., Alafnan, A., & Younes, K. M. (2023). Discovery of A Novel Synthetic Thiazole-benzimidazole Conjugate that Acts as a Potent Pancreatic Lipase Inhibitor using in silico and in vitro Approaches. Indian Journal of Pharmaceutical Education and Research, 57(1), 218–227. https://doi.org/10.5530/001954642131