2. Academic Validation
  3. A rationale approach in developing proline based small peptide as U-shaped analogues of arachidonic acid: Dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase for developing anti-inflammatory agents

A rationale approach in developing proline based small peptide as U-shaped analogues of arachidonic acid: Dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase for developing anti-inflammatory agents

  • Bioorg Chem. 2025 Jun 15:160:108452. doi: 10.1016/j.bioorg.2025.108452.
Vivesh Vivesh 1,  Priya Kumari 1,  Palwinder Singh 2
Affiliations

Affiliations

  • 1 Department of Chemistry, Guru Nanak Dev University Amritsar, 143005, India.
  • 2 Department of Chemistry, Guru Nanak Dev University Amritsar, 143005, India. Electronic address: palwinder.chem@gndu.ac.in.
PMID: 40253762 DOI: 10.1016/j.bioorg.2025.108452
Abstract

Guided by the molecular modelling studies, here, we report the development of small molecules containing Pro-Pro, Gly-Pro-Pro ester motifs as dual inhibitors of COX-2 and 5-LOX Enzymes. The synthesized compounds exhibited potent inhibitory activities against COX-2 and 5-LOX, with IC50 values in nanomolar range. Lineweaver-Burk plot analysis revealed that these molecules act as competitive inhibitors of COX-2 and 5-LOX. In vivo studies using the HET-CAM assay indicated that the compounds exhibit moderate to good anti-inflammatory effects. Hence, taking into account the physicochemical properties, including aqueous solubility, binding affinity to HSA and stability in blood plasma and liver microsomes, anti-inflammatory agents targeting dual pathways of arachidonic acid metabolism are identified.

Keywords

Anti-inflammatory; Arachidonic acid pathway; Inflammation; Small peptides.

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