{Reference Type}: Journal Article
{Title}: Insight on novel oxindole conjugates adopting different anti-inflammatory investigations and quantitative evaluation.
{Author}: Said MF;Marie SM;Mohamed NM;Mahrouse MA;Moussa BA;
{Journal}: Future Med Chem
{Volume}: 16
{Issue}: 9
{Year}: 2024 Apr 18
{Factor}: 4.767
{DOI}: 10.4155/fmc-2023-0318
{Abstract}: Background: A dual COX/5-LOX strategy was adopted to develop new oxindole derivatives with superior anti-inflammatory activity. Methods: Three series of oxindoles - esters 4a-p, 6a-l and imines 7a-o - were synthesized and evaluated for their anti-inflammatory and analgesic activities. Molecular docking and predicted pharmacokinetic parameters were done for the most active compounds. A new LC-MS/MS method was developed and validated for the quantification of 4h in rat plasma. Results: Compounds 4h, 6d, 6f, 6j and 7m revealed % edema inhibition up to 100.00%; also, 4l and 7j showed 100.00% writhing protection. Compound 4h showed dual inhibitory activity with IC50 = 0.0533 and 0.4195 μM for COX-2 and 5-LOX, respectively. Molecular docking rationalized the obtained biological activity. The pharmacokinetic parameters of 4h from rat plasma were obtained.<BR>[Box: see text].