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
Tlie inhibitory actions of ethyl acetate,n-butanol and water fractions from Actinidia chinensis Radix (A. chinensis Radix) ethanol extracts on glucosidase were investigated. We found that the inhibitory activity of di...Tlie inhibitory actions of ethyl acetate,n-butanol and water fractions from Actinidia chinensis Radix (A. chinensis Radix) ethanol extracts on glucosidase were investigated. We found that the inhibitory activity of different ethanol extract fractions on α-glucosidase is concentration-dependent. At the same concentration, the ethyl acetate and n-butaiiol fractions showed higher inliibitory activities on gglucosidase in comparison witli acarbose. We then determined the chemical constituents of tlie ethyl acetate and n-butanol fractions through ultra performance liquid cliromatography-triple-time of flight/mass spectrometry(UPLC-Triple-TOF/MS). Based on the mass spectrometry analysis and the databases Scitinder and Reaxys, 21 compoiinds(A1-A21) were identified from the ethyl acetate fraction. In addition, 11 of those compounds(A2, A3, A5, A6, A8, A10, A11, A13, A15, A19, A20) were identified for the first time from A. chinensis Radix. We also identified 14 compounds(A22-A32 and A4-A6) from tlie w-butanol fraction and compound A29 is a new natural product. From the n-butanol fraction, 7 additional compounds (A22, A25, A27, A28, A30-A32) were identified from A. chinensis Radix for the first time.展开更多
Oleandomycin glycosyltransferase variant P67T/S132F/A242V（ASP） was used to convert 10-hydroxycamptothecin into camptothecin-10-O-glucoside, which was confirmed by spectral analysis. Compared to the previously report...Oleandomycin glycosyltransferase variant P67T/S132F/A242V（ASP） was used to convert 10-hydroxycamptothecin into camptothecin-10-O-glucoside, which was confirmed by spectral analysis. Compared to the previously reported results, the present study reached the conversion rate up to 80% through the optimization of reaction conditions. In addition, compared with 10-hydroxycamptotheein（HCPT）, camptothecin-10-O-glucoside inhibited the proliferation of Huh7 cells in a concentration-dependent manner and showed stronger antineoplastic effect but lower toxicity. Furthermore, camptothecin-10-O-glucoside induced more apoptotic cells as compared with the parent compound.展开更多
Two series of novel spin-labeled derivatives of Cinobufagin（compounds 5 and 8a--8f in series 1 with five-membered ring nitroxyl free radical and compounds 6 and 9a-9f in series 2 with six-membered ring nitroxyl free ...Two series of novel spin-labeled derivatives of Cinobufagin（compounds 5 and 8a--8f in series 1 with five-membered ring nitroxyl free radical and compounds 6 and 9a-9f in series 2 with six-membered ring nitroxyl free radical） were synthesized. The cytotoxic activities in vitro against two tumor cell lines（HepG2 and HeLa） were evaluated, and the results indicate that all compounds display potent cytotoxicity against HepG2 and HeLa cells, and most compounds show better activities on HeLa cells than on HepG2 cells except for compounds 8a and 9d. Gene- rally, the compounds in series 2 have more potent cytotoxic activity against HepG2 than the compounds in series 1. Especially, compounds 6 and 9f in series 2 exhibit even more potent activities against the two tumor cell lines than Cinobufagin. Thus incorPoration of different L-amino acids as the linker changed the cytotoxic profile of the spin-labeled Cinobufagin. In addition, the representative compound 9f significantly changed the cell cycle distribution and led to HeLa cell cycle arrested at G2/M phase.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.
文摘Tlie inhibitory actions of ethyl acetate,n-butanol and water fractions from Actinidia chinensis Radix (A. chinensis Radix) ethanol extracts on glucosidase were investigated. We found that the inhibitory activity of different ethanol extract fractions on α-glucosidase is concentration-dependent. At the same concentration, the ethyl acetate and n-butaiiol fractions showed higher inliibitory activities on gglucosidase in comparison witli acarbose. We then determined the chemical constituents of tlie ethyl acetate and n-butanol fractions through ultra performance liquid cliromatography-triple-time of flight/mass spectrometry(UPLC-Triple-TOF/MS). Based on the mass spectrometry analysis and the databases Scitinder and Reaxys, 21 compoiinds(A1-A21) were identified from the ethyl acetate fraction. In addition, 11 of those compounds(A2, A3, A5, A6, A8, A10, A11, A13, A15, A19, A20) were identified for the first time from A. chinensis Radix. We also identified 14 compounds(A22-A32 and A4-A6) from tlie w-butanol fraction and compound A29 is a new natural product. From the n-butanol fraction, 7 additional compounds (A22, A25, A27, A28, A30-A32) were identified from A. chinensis Radix for the first time.
基金Supported by the National Natural Science Foundation of China（No. 81573315）, the Natural Science Foundation of Guangdong Province, China（No.2015A030313313）, the Guangzhou Industry University Collaborative Innovation Major Projects, China （No.201508030016） and the Natural Science Foundation of Hainan Province, China（No. 817307）.
文摘Oleandomycin glycosyltransferase variant P67T/S132F/A242V（ASP） was used to convert 10-hydroxycamptothecin into camptothecin-10-O-glucoside, which was confirmed by spectral analysis. Compared to the previously reported results, the present study reached the conversion rate up to 80% through the optimization of reaction conditions. In addition, compared with 10-hydroxycamptotheein（HCPT）, camptothecin-10-O-glucoside inhibited the proliferation of Huh7 cells in a concentration-dependent manner and showed stronger antineoplastic effect but lower toxicity. Furthermore, camptothecin-10-O-glucoside induced more apoptotic cells as compared with the parent compound.
基金Supported by the National Natural Science Foundation of China（No. 81573315）, the Natural Science Foundation of Guangdong Province, China（No.2015A030313313）, the Guangzhou Industry-University Collaborative Innovation Major Projects, China（No.201508030016） and the Natural Science Foundation of Hainan Province, China（No.817307）.
文摘Two series of novel spin-labeled derivatives of Cinobufagin（compounds 5 and 8a--8f in series 1 with five-membered ring nitroxyl free radical and compounds 6 and 9a-9f in series 2 with six-membered ring nitroxyl free radical） were synthesized. The cytotoxic activities in vitro against two tumor cell lines（HepG2 and HeLa） were evaluated, and the results indicate that all compounds display potent cytotoxicity against HepG2 and HeLa cells, and most compounds show better activities on HeLa cells than on HepG2 cells except for compounds 8a and 9d. Gene- rally, the compounds in series 2 have more potent cytotoxic activity against HepG2 than the compounds in series 1. Especially, compounds 6 and 9f in series 2 exhibit even more potent activities against the two tumor cell lines than Cinobufagin. Thus incorPoration of different L-amino acids as the linker changed the cytotoxic profile of the spin-labeled Cinobufagin. In addition, the representative compound 9f significantly changed the cell cycle distribution and led to HeLa cell cycle arrested at G2/M phase.
