Design, synthesis and biological screening of new 4-thiazolidinone derivatives with promising COX-2 selectivity, anti-inflammatory activity and gastric safety profile.
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 3h, respectively) in comparison with the reference drug celecoxib (S.I.=7.29, edema inhibition %=60 after 3h). 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.
['Abdellatif|Khaled R A|KR|', 'Abdelgawad|Mohamed A|MA|', 'Elshemy|Heba A H|HA|', 'Alsayed|Shahinda S R|SS|']
D000818:Animals D000893:Anti-Inflammatory Agents D000068579:Celecoxib D051545:Cyclooxygenase 1 D051546:Cyclooxygenase 2 D052246:Cyclooxygenase 2 Inhibitors D004487:Edema D006801:Humans D007052:Ibuprofen D051379:Mice D062105:Molecular Docking Simulation D012756:Sheep D013276:Stomach Ulcer D013449:Sulfonamides D053778:Thiazolidines
Anti-inflammatory Cyclooxygenase inhibition Molecular modeling Thiazolidinone