Discovery of new class of methoxy carrying isoxazole derivatives as COX-II inhibitors: Investigation of a detailed molecular dynamics study

• Published in: Journal of molecular structure Vol. 1157; pp. 19 - 28
• Main Authors: Joy, Monu, Elrashedy, Ahmed A., Mathew, Bijo, Pillay, Ashona Singh, Mathews, Annie, Dev, Sanal, Soliman, Mahmoud E.S., Sudarsanakumar, C.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 05.04.2018
• Subjects: Biological activity; Cyclooxygenase-II; Isoxazole; Molecular dynamics; Isoxazole; Molecular dynamics; LBDKSQDWAJOAMZ-UHFFFAOYSA-N; Cyclooxygenase-II; PVHMANUVEKMIBN-UHFFFAOYSA-N; Biological activity
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2017.11.109

Two novel isoxazole derivatives were synthesized and characterized by NMR and single crystal X-ray crystallography techniques. The methoxy and dimethoxy functionalized variants of isoxazole were screened for its anti-inflammatory profile using cyclooxygenase fluorescent inhibitor screening assay methods along with standard drugs, Celecoxib and Diclofenac. The potent and selective nature of the two isoxazole derivatives on COX-II isoenzyme with a greater magnitude of inhibitory concentration, as compared to the standard drugs and further exploited through molecular dynamics (MD) simulation. Classical, accelerated and multiple MD simulations were performed to investigate the actual binding mode of the two non-steroidal anti-inflammatory drug candidates and addressed their functional selectivity towards COX-II enzyme inhibitory nature. [Display omitted] •Synthesis of novel isoxazole derivatives through a newly developed protocol.•Complete structural elucidation through Crystallography.•Established selective COX-II inhibition through in vitro analysis.•Detailed binding mechanism was recognized with Docking and Molecular Dynamics approach.