Synthesis, Design and Anti-inflammatory Activity of Novel 5-(Indol-3-yl)thiazolidinone Derivatives as COX-2 Inhibitors

Background: New N-substituted 5-(oxoindolinyl)-2-thioxo- thiazolidinone derivatives were synthesized. Materials and Methods: The C-2-substituted thiazolidinone derivatives with piperidinyl and morpholinyl moieties in addition to the tetracyclic [(oxindolo)pyrazino]thiamlidine, the chloro- and amino- derivatives of the (indolyl)thiazolidinone ring system were also prepared. Results: The COX-2 inhibition activity of the synthesized compounds was investigated by studying their ability to inhibit the conversion of arachidonic acid to prostaglandin H2 (PGH2). Five of the tested candidates, substituted (oxonidolyl)thiazolidine derivatives (3a, 6f, 8b, 10 and 12) showed significant COX-2 inhibitory activity exhibiting IC50 values better than or close to the reference celecoxib. The anti-inflammatory activity was studied revealing that a number of compounds have shown good activities and compound 10 produced no significant mucosal injury. Conclusion: Molecular docking study was implemented to interpret the variable inhibitory activity of the newly synthesized compounds against COX enzyme. The results suggested that some of these derivatives could be active COX inhibitors possessing a high preference for COX-2.

Automated summary

New N-substituted 5-(oxoindolinyl)-2-thioxo-thiazolidinone derivatives were synthesized and tested for COX-2 inhibitory activity. Some of the compounds showed significant COX-2 inhibition and one compound demonstrated no significant mucosal injury. Molecular docking study revealed that some derivatives could be potential COX inhibitors with high preference for COX-2.