Abstract
Background Epilepsy poses a significant global health challenge,
particularly in regions with limited financial resources hindering access to
treatment. Recent research highlights neuroinflammation, particularly involving
cyclooxygenase-2 (COX-2) pathways, as a promising avenue for epilepsy
management.
Methods This study aimed to develop a Cyclooxygenase-2 inhibitor with
potential anticonvulsant properties. A promising drug candidate was identified
and chemically linked with phospholipids through docking analyses. The
activation of this prodrug was assessed using phospholipase A2 (PLA2)-mediated
hydrolysis studies. The conjugateʼs confirmation and cytotoxicity were evaluated
using Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning
Calorimetry (DSC), and Sulphoramide B (SRB) assays.
Results Docking studies revealed that the Celecoxib-Phospholipid conjugate
exhibited a superior affinity for PLA2 compared to other drug-phospholipid
conjugates. FT-IR spectroscopy confirmed the successful synthesis of the
conjugate, while DSC analysis confirmed its purity and formation. PLA2-mediated
hydrolysis experiments demonstrated selective activation of the prodrug
depending on PLA2 concentration. SRB experiments indicated dose-dependent
cytotoxic effects of Celecoxib, phospholipid non-toxicity, and efficient
celecoxib-phospholipid conjugation.
Conclusion This study successfully developed a Celecoxib-phospholipid
conjugate with potential anticonvulsant properties. The prodrugʼs specific
activation and cytotoxicity profile makes it a promising therapeutic candidate.
Further investigation into underlying mechanisms and in vivo studies is
necessary to assess its translational potential fully.
Keywords
epilepsy - phospholipase A2 - cyclooxygenase-2 inhibitor - conjugation
