Phenoxypropanolamine derivatives as selective inhibitors of the 20S proteasome beta 1 and beta 5 subunits

作者：Hovhannisyan Anna A; The Hien Pham; Bouvier Dominique; Tan Xiao; Touhar SiAmmar; Mkryan Gevorg G; Dallakyan Ashot M; El Amri Chahrazade; Melikyan Gagik S; Reboud Ravaux Michele; Bouvier Durand Michelle^*

来源：Bioorganic & Medicinal Chemistry Letters, 2017, 27(23): 5172-5178.

DOI：10.1016/j.bmcl.2017.10.055

• Phenoxypropanolamine
• Thiophene
• 20S proteasome
• ChT-L, T-L and PA activities
• Selective inhibition
• In silico structure-based docking

New series of thiophene-containing phenoxypropanolamines were synthesized and evaluated for their potency to inhibit the three proteolytic activities of the mammalian 20S proteasome. Noticeable inhibition of both ChT-L and PA activities was obtained with three compounds: one with unsubstituted phenoxypropanolamine group (7) and the two others with a p-Cl-substituted group (4 and 9). For three other compounds (3, 8 and 10), ChT-L activity alone was significantly inhibited. In silico docking performed on the beta 5 and beta 1 subunits bearing the respective ChT-L and PA catalytic sites showed features common to poses associated with active compounds. These features may constitute a selectivity criterion for structure-guided inhibitor design.

• 出版日期2017-12-1