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

摘要

Aim: A novel series of 2-arylimino-5-arylidenethiazolidin-4-ones 12a-n were synthesized and all the target compounds were fully characterized by IR, H-1 NMR, C-13 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. Results: Tested compounds were found more potent inhibitors of COX-2 (IC50 = 0.54-3.14 mu M) than COX-1 (IC50 = 4.97-11.52 mu M). The ulcerogenic liability of compounds 12(d, e, f, h, k, m) was performed and showed gastric safety more than or comparable to celecoxib. Conclusion: 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).