Pancreatic lipase inhibitory activity of selected pharmaceutical agents

• Published in: Acta Pharmaceutica 2019-03, Vol.69 (1), p.1-16
• Main Authors: Hamdan, Imad I., Kasabri, Violet N., Al-Hiari, Yusuf M., El-Sabawi, Dina, Zalloum, Hiba
• Format: Article
• Language: English
• Subjects: affinity capillary electrophoresis; Animals; Binding sites; Camphor; Capillary electrophoresis; Cefuroxime; docking studies; Electrophoresis; Enzyme Inhibitors - pharmacology; Lipase; Lipase - antagonists & inhibitors; Molecular interactions; Orlistat - pharmacology; Orphenadrine; Pancreas; Pancreas - metabolism; pancreatic lipase; pancreatic lipase inhibitory test; pharmaceutical compounds; Pharmaceutical Preparations - chemistry; Pharmaceuticals; Pharmacology; Salicylic acid; Structure-Activity Relationship; Sulfacetamide; Sulfonic acid; Surface activity; Swine; Synergistic effect
• ISSN: 1846-9558; 1330-0075; 1846-9558
• DOI: 10.2478/acph-2019-0010

Twenty-five structurally diverse compounds have been tested for their pancreatic lipase (PL) inhibitory activity. Despite the diversity of tested compounds, the relationship comprising structural attributes of the compounds could be established to correlate with the observed inhibitory activity. Compounds that exerted inhibitory action through surface activity were of different profile from the rest of compounds. When co-incubated with orlistat (OsT), important synergistic effects for some compounds (orphenadrine, gliclazide, cefuroxime and sulfacetamide) were revealed, while antagonistic effects were demonstrated for others (camphor sulfonic acid and dinitro salicylic acid). Docking studies for the most active molecules were performed and molecular interaction forces with the PL active site were identified. The results suggested co-binding of OsT along with the other inhibitor in the binding site in cases of synergistic effect but not in the case of antagonistic effect. These results were additionally supported by affinity capillary electrophoresis. In conclusion, synergistic lipase inhibitory activity between OsT and some other pharmaceutical compounds was demonstrated for the first time, which might help improve the pharmacological effect of OsT.