Synthesis of novel pancreatic lipase inhibitors: Biological investigation and in silico studies

Abstract

The targeted compounds which are Schiff base derivatives were prepared by reaction of 6-(4-phenyl-piperazin-1-yl)pyridine-3-ylamine with 2-hydroxy and 2,6-dichloro benzaldehyde. These compounds were isolated, purified and then spectrally characterized via FT-IR, ¹H and ¹³C NMR, LC MS TOF, and TGA analysis where strong proofs confirmed the formation of the targeted product. The biological activity, which is pancreatic porcine lipase inhibition, of the compounds was investigated and Orlistat was used as standard drug. The compound 3 was found to be as potent as orlistat against PL enzyme with an IC₅₀ value of 0.50 μM. The molecular docking studies were performed for both obtained compounds and orlistat against active side of porcine pancreatic lipase. Also, MM/PBSA binding free energy and molecular dynamics (MD) simulation analyzes were performed for pancreatic porcine lipase with compound 3, which showed potent inhibition according to the results of in vitro studies. Furthermore, The ADME and toxicity analysis of the compounds were examined using web-based online platforms, SwissADME and pkCSM. In the light of biological activity and in silico studies, the compound 3 can be a potential drug candidate with further studies.

Communicated by Ramaswamy H. Sarma

Keywords:

• ADMET
• antilipase activity
• molecular docking
• phenyl-piperazin
• Schiff base

Acknowledgement

The numerical calculations reported in this abstract were performed at The Scientific and Technological Research Council of Turkey (TUBITAK) ULAKBIM High Performance and Grid Computing Center (TRUBA resources).

Disclosure statement

All authors declare that they have no conflict of interest.