Tetra-substituted pyrazole analogues: synthesis, molecular docking, ADMET prediction, antioxidant and pancreatic lipase inhibitory activities


Cetin A., Dönmez A., Dalar A., Bildirici İ.

MEDICINAL CHEMISTRY RESEARCH, vol.32, no.1, pp.189-204, 2023 (SCI-Expanded)

  • Publication Type: Article / Article
  • Volume: 32 Issue: 1
  • Publication Date: 2023
  • Journal Name: MEDICINAL CHEMISTRY RESEARCH
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED)
  • Page Numbers: pp.189-204
  • Van Yüzüncü Yıl University Affiliated: Yes

Abstract

The development of novel analogues for the pancreatic lipase (PL) inhibitors and antioxidant candidates remains a significant research objective, as these studies are essential to our understanding of the role of PL receptor in obesity. Herein, we report on the synthesis, molecular docking, absorption, distribution, metabolism, excretion and toxicity (ADMET) properties, and biological evaluation of ten tetra-substituted pyrazole analogues as agents of PL inhibitors and antioxidant activities. The tetra-substituted pyrazole analogues displayed good binding affinity against Folin-Ciocalteu Reducing (FCR), Ferric Reducing Antioxidant Power (FRAP). However, the synthesized analogues displayed low binding affinity against Oxygen Radical Absorbance Capacity (ORAC). The tetra-substituted pyrazole analogues exhibited effective PL inhibition in the range of 2.0 ± 0.0 and 34.3 ± 0.3 μM according to the enzyme assays. Furthermore, the detailed interactions and binding energies of the PL-tetra-substituted pyrazole analogues’ complexes were determined using molecular docking studies. The binding energies of the PL-tetra-substituted pyrazole analogues’ complexes were found in range of 9.4 to 13.2 kcal/mol. In addition, the ADMET predictions of tetra-substituted pyrazole analogues were carried out using PreADMET software. Overall, the obtained results revealed that antioxidant and PL inhibitory activities of tetra-substituted pyrazole analogues were in consensus with the ADMET predictions results.