Design, synthesis and biological screening of new 4-thiazolidinone derivatives with promising COX-2 selectivity, anti-inflammatory activity and gastric safety profile

• Two groups of thiazolidin-4-ones 4a–c and 8a–e were designed and synthesized.
• Compounds 8c and 8d showed the best overall in vitro COX-2 selectivity and in vivo activities.
• 8c and 8d showed reduction in ulcerogenic potential versus celecoxib = 85%, 92% respectively.
• 8c and 8d could be used as a lead compound for developing new anti-inflammatory agents.

Two series of new thiazolidin-4-one derivatives 4a–c and 8a–e were designed and prepared. All the synthesized compounds were evaluated for their in vitro COX-2 selectivity and anti-inflammatory activity in vivo. Compounds 8c and 8d showed the best overall in vitro COX-2 selectivity (selectivity indexes of 4.56 and 5.68 respectively) and in vivo activities (edema inhibition % = 61.8 and 67 after 3 h, respectively) in comparison with the reference drug celecoxib (S.I. = 7.29, edema inhibition % = 60 after 3 h). In addition, 8c and 8d were evaluated for their mean effective anti-inflammatory doses (ED50 = 27.7 and 18.1 μmol/kg respectively, celecoxib ED50 = 28.2 μmol/kg) and ulcerogenic liability (reduction in ulcerogenic potential versus celecoxib = 85%, 92% respectively. Molecular docking studies were performed and the results were in agreement with that obtained from the in vitro COX inhibition assays.

Figure optionsDownload as PowerPoint slide