Exploring the Anticonvulsant Properties of a Celecoxib-Phospholipid Conjugate: Synthesis, Activation, and Evaluation of Cytotoxicity.

Autor:	Anjali PB; Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, The Nilgiris, Tamil Nadu, India., Jawahar N; Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, The Nilgiris, Tamil Nadu, India., Praharsh Kumar MR; Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, The Nilgiris, Tamil Nadu, India., Jubie S; Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, The Nilgiris, Tamil Nadu, India., Selvamuthukumar S; Deparment of Pharmacy, Annamalai University, Annamalai Nagar, Chidambaram, Tamil Nadu, India.
Jazyk:	angličtina
Zdroj:	Drug research [Drug Res (Stuttg)] 2024 Jul; Vol. 74 (6), pp. 296-301. Date of Electronic Publication: 2024 Jul 05.
DOI:	10.1055/a-2331-7114
Abstrakt:	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 conjugate's 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 prodrug's 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. Competing Interests: The authors declare that they have no conflict of interest. (Thieme. All rights reserved.)
Databáze:	MEDLINE
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