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

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...

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Detalles Bibliográficos
Autores principales: Farn, Shiou-Shiow, Lai, Yen-Buo, Hua, Kuo-Fong, Chen, Hsiang-Ping, Yu, Tzu-Yi, Lo, Sheng-Nan, Shen, Li-Hsin, Sheu, Rong-Jiun, Yu, Chung-Shan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9105197/
https://www.ncbi.nlm.nih.gov/pubmed/35566202
http://dx.doi.org/10.3390/molecules27092850
Descripción
Sumario: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.