Synthesis, biological evaluation, molecular docking and theoretical evaluation of ADMET properties of nepodin and chrysophanol derivatives as potential cyclooxygenase (COX-1, COX-2) inhibitors

被引：48

作者：

Grover, Jagdeep ^{[1
]}

Kumar, Vivek ^{[2
]}

Singh, Vikram ^{[1
]}

Bairwa, Khemraj ^{[1
]}

Sobhia, M. Elizabeth ^{[2
]}

Jachak, Sanjay M. ^{[1
]}

机构：

[1] Natl Inst Pharmaceut Educ & Res, Dept Nat Prod, Sas Nagar 160062, Punjab, India

[2] Natl Inst Pharmaceut Educ & Res, Dept Pharmacoinformat, Sas Nagar 160062, Punjab, India

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 80卷

关键词：

Nepodin; Chrysophanol; COX inhibitors; Anti-inflammatory; Molecular docking; PROSTAGLANDIN BIOSYNTHESIS; ANTIINFLAMMATORY AGENTS; VALIDATION; DESIGN;

D O I：

10.1016/j.ejmech.2014.04.033

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Nepodin and chrysophanol, isolated from Rumex nepalensis roots, showed significant cyclooxygenase (COX) inhibitory activity. To further optimize these lead molecules and study structure activity relationship (SAR), eighteen derivatives of nepodin and nine derivatives of chrysophanol were synthesized and evaluated for COX-1 and COX-2 inhibitory potential. Among the synthesized compounds, four nepodin (1f, 1g, 1h and 1i) and three chrysophanol (2e, 2f and 2h) derivatives displayed more pronounced COX-2 inhibition than their respective lead molecule. Further, compounds 1f, 1g, 2e and 2h exhibited better anti-inflammatory activity than ibuprofen in carrageenan-induced rat paw edema assay. Taking into account the in vitro and in vivo results, molecular docking and in silico prediction of ADMET properties of compounds were carried out respectively. (C) 2014 Elsevier Masson SAS. All rights reserved.

引用

页码：47 / 56

页数：10

共 23 条

[1] An NMR, IR and theoretical investigation of 1H Chemical Shifts and hydrogen bonding in phenols [J].