A new series of N-5 derivatives of the 1,1,5-trimethyl furo[3,4-c]pyridine-3,4-dione (cerpegin) selectively inhibits the post-acid activity of mammalian 20S proteasomes

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Pham, The Hien | Hovhannisyan, Anna | Bouvier, Dominique | Tian, Lei | Reboud-Ravaux, Michele | Melikyan, Gagik | Bouvier-Durand, Michelle

Edité par CCSD ; Elsevier -

International audience. A large set of N-5-derivatives of cerpegin (1,1,5-trimethyl furo[3,4-c]pyridine-3,4-dione) was designed and synthesized in high yields by a simple and handy method using various primary amines for a pyridine cycle synthesis. The effects of 29 derivatives on the three types of catalytic sites of purified mammalian 20S proteasomes (CT-L, T-L and PA) were measured. Most of the new compounds specifically inhibited the PA activity, in the micromolar range. Docking experiments support these results. Moreover, neither calpain I nor cathepsin B were inhibited.

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