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

被引：63
作者：
Abdellatif, Khaled R. A. [1 ]
Abdelgawad, Mohamed A. [1 ,2 ]
Elshemy, Heba A. H. [1 ]
Alsayed, Shahinda S. R. [1 ]
机构：
[1] Beni Suef Univ, Dept Organ Pharmaceut Chem, Bani Suwayf 62514, Egypt
[2] Al Jouf Univ, Coll Pharm, Dept Pharmaceut Chem, Al Jouf 2014, Saudi Arabia
来源：
BIOORGANIC CHEMISTRY | 2016年 / 64卷
关键词：
Thiazolidinone; Cyclooxygenase inhibition; Anti-inflammatory; Molecular modeling; DONOR ESTER PRODRUGS; CYCLOOXYGENASE-2; INHIBITORS; CELECOXIB ANALOGS; DUAL INHIBITORS; DISCOVERY; MOIETY; POTENT;
D O I：
10.1016/j.bioorg.2015.11.001
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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 mu mol/kg respectively, celecoxib ED50 = 28.2 mu mol/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. (C) 2015 Elsevier Inc. All rights reserved.
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页码：1 / 12
页数：12
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