Some cinobufagin oxime ether derivatives as potential Na＋/K＋-ATPase inkibitors were synthesized by following the side chain of istaroxime. These compounds inhibit Na＋/K＋-ATPase in a dose-dependent manner. Compound...Some cinobufagin oxime ether derivatives as potential Na＋/K＋-ATPase inkibitors 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 inhibi- tion, which was stronger than compound 3a with only hydroxyoxime moiety at C3 and compound 3b with a methy-lated 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 C3 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.展开更多
基金Supported by the National Natural Science Foundation of China（No.81573315）, the Guangdong Natural Science Fund, China（No.2015A030313313） and the Guangzhou Industry-University Collaborative Innovation Major Projects, China（No. 201508030016）.
文摘Some cinobufagin oxime ether derivatives as potential Na＋/K＋-ATPase inkibitors 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 inhibi- tion, which was stronger than compound 3a with only hydroxyoxime moiety at C3 and compound 3b with a methy-lated 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 C3 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.
