Design, synthesis, and biological evaluation of substituted hydrazone and pyrazole derivatives as selective COX-2 inhibitors: Molecular docking study

详细信息    查看全文

• 作者：Magda A.-A. El-Sayed^a ; Naglaa I. Abdel-Aziz^b ; ^{naglaabdalaziz2005@yahoo.com"" rel=""nofollow} ; Alaa A.-M. Abdel-Aziz^b ; ^c ; Adel S. El-Azab^c ; ^d ; Yousif A. Asiri^e ; Kamal E.H. ElTahir^f
• 关键词：Hydrazone and pyrazole derivatives ; Selective COX-2 inhibitors ; Molecular docking
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2011
• 出版时间：1 June 2011
• 年：2011
• 卷：19
• 期：11
• 页码：3416-3424
• 全文大小：704 K

文摘

New arylhydrazone derivatives and a series of 1,5-diphenyl pyrazoles were designed and synthesized from 1-(4-chlorophenyl)-4,4,4-trifuorobutane-1,3-dione 1. The newly synthesized compounds were investigated in vivo for their anti-inflammatory activities using carrageenan-induced rat paw oedema model. Moreover, they were tested for their inhibitory activity against ovine COX-1 and COX-2 using an in vitro cyclooxygenase (COX) inhibition assay. Some of the new compounds (2f, 6a and 6d) showed a reasonable in vitro COX-2 inhibitory activity, with IC₅₀ value of 0.45 μM and selectivity index of 111.1. A virtual screening was carried out through docking the designed compounds into the COX-2 binding site to predict if these compounds have analogous binding mode to the COX-2 inhibitors. Docking study of the synthesized compounds 2f, 6a and 6d into the active site of COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor.