Novel cinobufagin oxime ether derivatives as potential Na⁺/K⁺-ATPase inhibitors: Synthesis, biological screening and molecular docking

Abstract

Some cinobufagin oxime ether derivatives as potential Na⁺/K⁺-ATPase inhibitors were synthesized by following the side chain of istaroxime. These compounds inhibit Na⁺/K⁺-ATPase in a dose-dependent manner. Compound 3c with an oxyethylamine side chain that is the same as that of istaroxime showed the most potent inhibition, which was stronger than compound 3a with only hydroxyoxime moiety at C-3 and compound 3b with a methylated hydroxyoxime moiety. Molecular docking was used to explore the binding modes of the target compounds with Na⁺/K⁺-ATPase, which suggested that the longer ethyl amine group at C-3 oxime moiety of compound 3c could make stronger interaction with Na⁺/K⁺-ATPase via intermolecular charge-charge and H-bond interaction as compared with other derivatives.

Keywords

Cinobufagin / Istaroxime / Na⁺/K⁺-ATPase / Molecular docking

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