ABSTRACT:
Over the last four dacades, obesity has emerged as a significant globale health issue, closely associated with several serious condition including diabetes and heart diseases. Alarmingly, the prevalence of obesity continues to rise each year, and effective solutions seem elusive. While various strategies and medications have been introduced to tackle obesity and support weight loss; many of these options come with drawbacks, such as the risk of malnutrition and inconsistent results due to limited effectiveness. In this study, we will adopt a molecular modelling approach using pharmacophore based virtual screening and molecular docking studies to design potential oral pancreatic lipase inhibitors which prevent excess fatty acid absorption and promotes weight loss, all while minimizing intestinal absorption to avoid possible systemic side effects.
Cite this article:
Alchab Faten. Developing of a new Pharmacophore Containing Sulfonyl Fluoride Group as Potential Gastrointestinal Lipase Inhibitors. Research Journal of Pharmacy and Technology.2025;18(2):831-8. doi: 10.52711/0974-360X.2025.00123
Cite(Electronic):
Alchab Faten. Developing of a new Pharmacophore Containing Sulfonyl Fluoride Group as Potential Gastrointestinal Lipase Inhibitors. Research Journal of Pharmacy and Technology.2025;18(2):831-8. doi: 10.52711/0974-360X.2025.00123 Available on: https://rjptonline.org/AbstractView.aspx?PID=2025-18-2-55
REFERENCES:
1. Panuganti, K.K., M. Nguyen, and R.K. Kshirsagar. Obesity, in StatPearls. 2024, StatPearls Publishing
2. The World Health Organization. Feb 2024]; Available from: https://www.who.int/.
3. Apovian, C.M. Obesity: definition, comorbidities, causes, and burden. Am J Manag Care. 2016. 22(7 Suppl): p. s176-85.
4. Lin, X. and H. Li. Obesity: Epidemiology, Pathophysiology, and Therapeutics. Front Endocrinol (Lausanne). 2021; 12: 706978. https://doi.org/10.3389/fendo.2021.706978
5. S. N. C, S., S. Palawat, and A.T. Paul. Design, synthesis, biological evaluation and molecular modelling studies of conophylline inspired novel indolyl oxoacetamides as potent pancreatic lipase inhibitors. New Journal of Chemistry. 2020; 44(28): 12355-12369. https://doi.org/10.1039/D0NJ02622K
6. Bansal, A.B. and Y. Al Khalili. Orlistat, in StatPearls. 2024; StatPearls Publishing
7. Valladales-Restrepo, L.F., et al. Effectiveness, persistence of use, and safety of orlistat and liraglutide in a group of patients with obesity. Expert Opin Pharmacother. 2023; 24(4): 535-543. https://doi.org/10.1080/14656566.2023.2178900
8. Diseases, B.M.N.I.o.D.a.D.a.K. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. 2012-2024.
9. Mukherjee, M. Human digestive and metabolic lipases—a brief review. Journal of Molecular Catalysis B: Enzymatic. 2003; 22(5): 369-376. https://doi.org/https://doi.org/10.1016/S1381-1177(03)00052-3
10. Zhang, J., et al. Design, Synthesis, and Structure-Activity Relationship Study of Pyrazolones as Potent Inhibitors of Pancreatic Lipase. ChemMedChem. 2021; 16(10): 1600-1604. https://doi.org/https://doi.org/10.1002/cmdc.202000850
11. Birari, R.B. and K.K. Bhutani. Pancreatic lipase inhibitors from natural sources: unexplored potential. Drug Discov Today. 2007; 12(19-20): 879-89. https://doi.org/10.1016/j.drudis.2007.07.024
12. Colin, D.Y., et al. Exploring the active site cavity of human pancreatic lipase. Biochemical and Biophysical Research Communications. 2008; 370(3): 394-398. https://doi.org/https://doi.org/10.1016/j.bbrc.2008.03.043
13. Kumar, A. and S. Chauhan. Pancreatic lipase inhibitors: The road voyaged and successes. Life Sciences. 2021; 271: 119115. https://doi.org/https://doi.org/10.1016/j.lfs.2021.119115
14. Lunagariya, N.A., et al. Inhibitors of pancreatic lipase: state of the art and clinical perspectives. Excli j. 2014; 13: 897-921.
15. Narayanan, A. and L.H. Jones, Sulfonyl fluorides as privileged warheads in chemical biology. Chem Sci. 2015; 6(5): 2650-2659. https://doi.org/10.1039/c5sc00408j
16. Carneiro, S.N., et al. Sulfur(vi) fluorides as tools in biomolecular and medicinal chemistry. Organic and Biomolecular Chemistry. 2023; 21(7): 1356-1372. https://doi.org/10.1039/D2OB01891H
17. Tian, Y., et al. Efficient screening of pancreatic lipase inhibitors from cod meat hydrolysate through ligand fishing strategy. Front Nutr. 2022; 9: 969558. https://doi.org/10.3389/fnut.2022.969558
18. Thomas, A., et al. Role of the Lid Hydrophobicity Pattern in Pancreatic Lipase Activity. Journal of Biological Chemistry. 2005; 280(48): 40074-40083. https://doi.org/https://doi.org/10.1074/jbc.M502123200
19. Samual, T. A comprehensive review on the pancreatic lipase inhibitory peptides: A future anti-obesity strategy. Electronic Journal of General Medicine. 2023; 20: 2516-3507. https://doi.org/10.29333/ejgm/12943
20. Group, C.C. Molecular Operating Environment. 2022.
21. Biovia, D.S., Discovery Studio 2016, San Diego: Dassault Systèmes. 2016.
22. Shivanyuk, A., et al. Enamine real database: Making chemical diversity real. Chimica Oggi. 2007; 25: 58-59.
23. Berman, H.M., et al. The Protein Data Bank. Nucleic Acids Research. 2000; 28(1): 235-242. https://doi.org/10.1093/nar/28.1.235
24. The RCSB Protein database. 19 October 2023]; Available from: http://www.rcsb.org/.
25. Colin, D.Y., et al. Modification of pancreatic lipase properties by directed molecular evolution. Protein Engineering, Design and Selection. 2010; 23(5): 365-373. https://doi.org/10.1093/protein/gzq008
26. Case, D.A., et al. The Amber biomolecular simulation programs. J Comput Chem. 2005; 26(16): 1668-88. https://doi.org/10.1002/jcc.20290