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

Mermer A., Demirci S., TATAR G.

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, vol.40, no.2, pp.931-940, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 40 Issue: 2
  • Publication Date: 2022
  • Doi Number: 10.1080/07391102.2021.1950573
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE
  • Page Numbers: pp.931-940
  • Keywords: ADMET, antilipase activity, molecular docking, phenyl-piperazin, Schiff base, FOOD-INTAKE, DERIVATIVES, DESIGN, OBESITY, CONSEQUENCES, CONSTITUENTS, MOLECULES, WEIGHT, BASES, RISK
  • Karadeniz Technical University Affiliated: Yes


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, H-1 and C-13 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 mu M. 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