Antiinflammation Derived Suzuki-Coupled Fenbufens as COX-2 Inhibitors: Minilibrary Construction and Bioassay

Molecules

Tzu-Yi Yu¹  Yen-Buo Lai¹  Shiou-Shiow Farn¹  Li-Hsin Shen¹  Chung-Shan Yu¹  Hsiang-Ping Chen¹  Kuo-Fong Hua²  Rong-Jiun Sheu³  Sheng-Nan Lo⁴ 

[1] Department of Biomedical Engineering and Environmental Sciences, National Tsinghua University, Hsinchu 30013, Taiwan;Department of Biotechnology and Animal Science, National Ilan University, Ilan 26007, Taiwan;Institute of Nuclear Engineering and Science, National Tsinghua University, Hsinchu 30013, Taiwan;Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan 32546, Taiwan;

关键词: COX-2 selectivity;    synergistic;    COVID-19;    biaryl;    inflammasome;   

DOI  :  10.3390/molecules27092850

来源: DOAJ

【 摘 要 】

A small fenbufen library comprising 18 compounds was prepared via Suzuki Miyara coupling. The five-step preparations deliver 9–17% biphenyl compounds in total yield. These fenbufen analogs exert insignificant activity against the IL-1 release as well as inhibiting cyclooxygenase 2 considerably. Both the para-amino and para-hydroxy mono substituents display the most substantial COX-2 inhibition, particularly the latter one showing a comparable activity as celecoxib. The most COX-2 selective and bioactive disubstituted compound encompasses one electron-withdrawing methyl and one electron-donating fluoro groups in one arene. COX-2 is selective but not COX-2 to bioactive compounds that contain both two electron-withdrawing groups; disubstituted analogs with both resonance-formable electron-donating dihydroxy groups display high COX-2 activity but inferior COX-2 selectivity. In silico simulation and modeling for three COX-2 active—p-fluoro, p-hydroxy and p-amino—fenbufens show a preferable docking to COX-2 than COX-1. The most stabilization by the p-hydroxy fenbufen with COX-2 predicted by theoretical simulation is consistent with its prominent COX-2 inhibition resulting from experiments.

【 授权许可】

Unknown