Pancreatic lipase inhibitory activity of selected pharmaceutical agents

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. Com...

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Bibliographic Details
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
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
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Summary: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.
ISSN:1846-9558
1330-0075
1846-9558
DOI:10.2478/acph-2019-0010