Design and Development of COX-II Inhibitors: Current Scenario and Future Perspective

被引:14
作者
Chahal, Sandhya [1 ]
Rani, Payal [1 ]
Kiran, Gaurav
Sindhu, Jayant [1 ]
Joshi, Gaurav [2 ,3 ]
Ganesan, Aravindhan [4 ]
Kalyaanamoorthy, Subha [5 ]
Mayank, Rajvir
Kumar, Parvin [6 ]
Singh, Rajvir [1 ]
Negi, Arvind [7 ]
机构
[1] CCS Haryana Agr Univ, COBS&H, Dept Chem, Hisar 125004, India
[2] Hemvati Nandan Bahuguna Garhwal, Dept Pharmaceut Sci, Tehri Garhwal 249161, Uttarakhand, India
[3] Grap Era Deemed Univ, Dept Biotechnol, Dehra Dun 248002, Uttarakhand, India
[4] Univ Waterloo, Sch Pharm, ArGansLab, Waterloo, ON N2G 1C5, Canada
[5] Univ Waterloo, Dept Chem, Waterloo, ON N2L 3G1, Canada
[6] Kurukshetra Univ, Dept Chem, Kurukshetra 136119, India
[7] Aalto Univ, Sch Chem Engn, Dept Bioprod & Biosyst, Espoo 02150, Finland
来源
ACS OMEGA | 2023年 / 8卷 / 20期
关键词
DIHYDROPYRAZOLE SULFONAMIDE DERIVATIVES; BIOLOGICAL EVALUATION; ANTIINFLAMMATORY ACTIVITY; MOLECULAR DOCKING; CYCLOOXYGENASE-2; COX-2; IN-VITRO; PYRAZOLE DERIVATIVES; PGE(2) PRODUCTION; DUAL INHIBITION; QSAR ANALYSIS;
D O I
10.1021/acsomega.3c00692
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Innate inflammation beyond a threshold is a significant problem involved in cardiovascular diseases, cancer, and many other chronic conditions. Cyclooxygenase (COX) enzymes are key inflamma -tory markers as they catalyze prostaglandins production and are crucial for inflammation processes. While COX-I is constitutively expressed and is generally involved in "housekeeping" roles, the expression of the COX -II isoform is induced by the stimulation of different inflammatory cytokines and also promotes the further generation of pro-inflammatory cytokines and chemokines, which affect the prognosis of various diseases. Hence, COX-II is considered an important therapeutic target for drug development against inflammation-related illnesses. Several selective COX-II inhibitors with safe gastric safety profiles features that do not cause gastrointestinal complications associated with classic anti-inflammatory drugs have been developed. Nevertheless, there is mounting evidence of cardiovascular side effects from COX-II inhibitors that resulted in the withdrawal of market-approved anti-COX-II drugs. This necessitates the development of COX-II inhibitors that not only exhibit inhibit potency but also are free of side effects. Probing the scaffold diversity of known inhibitors is vital to achieving this goal. A systematic review and discussion on the scaffold diversity of COX inhibitors are still limited. To address this gap, herein we present an overview of chemical structures and inhibitory activity of different scaffolds of known COX-II inhibitors. The insights from this article could be helpful in seeding the development of next-generation COX-II inhibitors.
引用
收藏
页码:17446 / 17498
页数:53
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