Discovery of a COX-2 selective inhibitor hit with anti-inflammatory activity and gastric ulcer protective effect

A novel series of 2-arylimino-5-arylidenethiazolidin-4-ones 12a-n were synthesized and all the target compounds were fully characterized by IR, ¹H NMR, ¹³C NMR, mass spectroscopy and elemental analysis. Materials & methods: All the target compounds were evaluated for their COX inhibition by enzyme immunoassay kit and in vivo anti-inflammatory activity.

Tested compounds were found more potent inhibitors of COX-2 (IC₅₀ = 0.54-3.14 µM) than COX-1 (IC₅₀ = 4.97-11.52 µM). The ulcerogenic liability of compounds 12(d, e, f, h, k, m) was performed and showed gastric safety more than or comparable to celecoxib.

In addition, docking study of the most potent and selective compound 12h into COX-2 active site revealed that this target compound assumed interactions and binding pattern similar to that of as a cocrystallized ligand bromocelecoxib (S-58).