Year: 2026
Type: article
Abstract: The development of cyclooxygenase-2 (COX-2) inhibitors plays a key role in developing safer anti-inflammatory therapies. The study based on the examination of a celecoxib-derived compound (T1) to analyse its potential as a COX-2 inhibitor. Density functional theory (DFT) calculations were carried out to optimize the molecular geometry and evaluate the electronic structure parameters of the designed compound. HOMO and LUMO energies (Frontier molecular orbital) were extracted from the optimized output files. These were utilised to calculate global reactivity descriptors including, ionization energy, electron affinity and electronegativity. The potential energy scan showed the proton transfer reaction and the stability of keto form in the excited state. Molecular docking analysis showed that the designed ligand fits well within the hydrophobic channel of the COX-2 enzyme. The binding pocket is mainly surrounded by hydrophobic amino acid residues including, Phe381, Leu352, Val349, Val523, Ala527, Leu384 and Phe518. The molecular dynamics studies showed that the compound forms a stable complex with COX-2 during the 100 ns simulation. The protein maintains its structural stability and the ligand remains bound within the active site. Overall, the combined results supporting its potential as a selective COX-2 inhibitor and providing a foundation for future experimental validation that can help in the design of safer and more effective anti-inflammatory drugs.
Authors: Kusum ., Gulshan Singh, Anjali Ahlawat, Vijay Dangi
Institutions: Baba Mastnath University, Gurugram University
Language: English
Subfield: Drug Discovery
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7143501005