Anti-inflammatory indomethacin analogs endowed with preferential COX-2 inhibitory activity

被引：20

作者：

Amin, Noha H. ^{[1
]}

El-Saadi, Mohammed T. ^{[1
]}

Hefny, Ahmed A. ^{[1
]}

Abdelazeem, Ahmed H. ^{[1
,2
]}

Elshemy, Heba A. H. ^{[3
]}

Abdellatif, Khaled R. A. ^{[3
,4
]}

机构：

[1] Beni Suef Univ, Dept Med Chem, Fac Pharm, Bani Suwayf 62514, Egypt

[2] Al Rayyan Coll, Coll Med, Al Madinah Al Munawarah 41411, Saudi Arabia

[3] Beni Suef Univ, Fac Pharm, Dept Pharmaceut Organ Chem, Bani Suwayf 62514, Egypt

[4] Ibn Sina Natl Coll Med Studies, Pharmaceut Sci Dept, Jeddah 21418, Saudi Arabia

来源：

FUTURE MEDICINAL CHEMISTRY | 2018年 / 10卷 / 21期

关键词：

anti-inflammatory; celecoxib; cyclooxygenase; docking; indole; indomethacin; Lipinski; molecular; ulcer; BIOLOGICAL EVALUATION; CYCLOOXYGENASE INHIBITION; ULCEROGENIC LIABILITY; DERIVATIVES; DESIGN; INDOLE; DOCKING;

D O I：

10.4155/fmc-2018-0224

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

Aim: The undeniable indomethacin potency has always suffered serious obstacles such as gastric damage. Continuous attempts to develop potent yet safe indomethacin analogs have never ceased. Results: Herein are new indole derivatives 4a-h and 5a-c, which were synthesized via Fisher indole reaction, evaluated for both their in vivo anti-inflammatory activities using rat paw edema method and their in vitro cyclooxygenase inhibitory activities. Then ulcerogenic liability, physicochemical parameters and molecular docking modeling were performed for the most potent ones. Conclusion: Promising results were obtained, where compound 4f was the best anti-inflammatory agent and preferential COX-2/COX-1 inhibitor (90.5% edema inhibition, selective index = 65.71, ulcer index = 7.3), if compared with indomethacin (86.7% edema inhibition, selective index = 0.079, ulcer index = 20.20).

引用

页码：2521 / 2535

页数：15

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