Ukr.Biochem.J. 2025; Volume 97, Issue 4, Jul-Aug, pp. 84-93

doi: https://doi.org/10.15407/ubj97.04.084

In vivo, in vitro, and molecular docking study of rat pancreatic lipase inhibition using isopropyl salicylate

10.09.2025   Uncategorized   No comments

Noor M. Mahdi1, Sarah A. Younus2,
Abdallah F. Al-Burgus1, Omar Y. Al-Abbasy3*

1General Directorate of Education in Nineveh, Mosul, Iraq;
2Department of Chemistry and Biochemistry, College of Medicine,
University of Nineveh, Mosul, Iraq;
3Department of Chemistry, College of Education for Pure Science,
University of Mosul, Mosul, Iraq;
*e-mail: chem.omar1978@uomosul.edu.iq

Received: 30 April 2025; Revised: 11 July 2025;
Accepted: 12 September 2025; Available on-line: 17 September 2025

Pancreatic lipase (PL) represents a significant treatment target that has been the focus of research on anti-obesity medications. Orlistat is the only regularly used prescription that has been approved for long-term use. The discovery of new compounds for anti-obesity treatment based on PL inhibition can be achieved, in particular, by structure-based virtual screening with docking software. The aim of this research was to study isopropyl salicylate (IPS) anti-hyperlipidemic activity and inhibitory effect on rat pancreatic PL in comparison with orlistat. Wistar rats were divided into four groups of 8 animals each: control; fed with a high-fat diet (HFD) for 12 weeks to produce hyperlipidemia; fed with HFD and Orlistat (10 mg/kg BW daily); fed with HFD and IPS (10.81 mg/kg BW daily). It was shown that BW gain and lipase activity in the plasma of the high-fat diet rats treated with either orlistat or isopropyl salicylate were reduced considerably compared with untreated rats. The pancreatic lipase was partially purified from the plasma of obese rats, and a kinetic study of the IPS effect identified a competitive inhibition mode with an assessed Ki of 30.53 mM. An in silico study of the interaction between IPS and rat pancreatic lipase-related protein 2 (PDB ID: 1BU8) was conducted. The binding energy value ΔG for the IPS-protein complex at the enzyme’s active site was found to be -5.4 kcal/mol, while that for the orlistat-protein complex was -4.4 kcal/mol, indicating the stronger interaction of the enzyme with isopropyl salicylate than with orlistat.

Keywords: , , , , , ,

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