title: Design, synthesis and biological screening of new 4-thiazolidinone derivatives with promising COX-2 selectivity, anti-inflammatory activity and gastric safety profile.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Organic Chemistry, Beni Suef University, Beni Suef 62514, Egypt. Electronic address: khaled.ahmed@pharm.bsu.edu.eg.
authors.forename: Khaled R A
authors.initials: KR
authors.lastname: Abdellatif
authors.affiliation: Department of Pharmaceutical Organic Chemistry, Beni Suef University, Beni Suef 62514, Egypt; Pharmaceutical Chemistry Department, College of Pharmacy, Al Jouf University, Sakaka, Al Jouf 2014, Saudi Arabia.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Abdelgawad
authors.affiliation: Department of Pharmaceutical Organic Chemistry, Beni Suef University, Beni Suef 62514, Egypt.
authors.forename: Heba A H
authors.initials: HA
authors.lastname: Elshemy
authors.affiliation: Department of Pharmaceutical Organic Chemistry, Beni Suef University, Beni Suef 62514, Egypt.
authors.forename: Shahinda S R
authors.initials: SS
authors.lastname: Alsayed
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000138:chemical synthesis / Q000627:therapeutic use*; D000068579:Celecoxib / Q000494:pharmacology / Q000627:therapeutic use; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000138:chemical synthesis / Q000627:therapeutic use*; D004487:Edema / Q000188:drug therapy; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D062105:Molecular Docking Simulation; D012756:Sheep; D013276:Stomach Ulcer / Q000139:chemically induced; D013449:Sulfonamides / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology*; D053778:Thiazolidines / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: C000613594:3-(4-aminosulfonylphenylamino)-2-(4-chlorophenyl)-5-methyl-4-thiazolidinone; C000613595:3-(4-aminosulfonylphenylamino)-2-(4-fluorophenyl)-5-methyl-4-thiazolidinone; D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D013449:Sulfonamides; D053778:Thiazolidines; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000068579:Celecoxib; D007052:Ibuprofen
keywords: Anti-inflammatory; Cyclooxygenase inhibition; Molecular modeling; Thiazolidinone