Digoxin derivatives substituted by alkylidene at the butenolide part

Xu, Haiwei; Liu, Gai-Zhi; Zhu, Song-Lin; Guang-feng, Hong; Liu, Hong‐Min; Wu, Qiong

doi:10.1016/j.steroids.2010.02.007

Cited by 9 publications

(2 citation statements)

References 11 publications

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“…Great progress has been achieved on structural modifications of cardenolides either in sugar or steroidal core part, but only a few reports could be found about the modification in the lactone part of cardenolides ,. A report of synthesized digoxin‐21‐salicylidene as a RORγt antagonist inspired us to explore the modification of uscharin upon its lactone part.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of 21‐Alkylidenes and 21‐Alkylol Analogues of Uscharin and Their Effects on Intracellular Calcium in Cardiac Cells

et al. 2019

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Five 21‐alkylidenes (2‐6) and a 21‐alkylol (7) derivatives of uscharin (1) were synthesized by aldol condensation reaction and aldol reaction of uscharin with aromatic aldehydes, respectively. We investigated the ability of uscharin and its derivatives to interfere with the intracellular calcium level by flow cytometry and contractile characteristics at the single cell level by time‐lapse microscopy in H9c2 cells. Changes of spontaneous calcium oscillations in beating HL‐1 cells were also studied by a high‐throughput Fluorometric Imaging Plate Reader (FLIPR) assay. We reported for the first time that uscharin could produce increased contraction strength in cardiac muscle cells while it showed a significant cytotoxicity to atrial cells. Unlike uscharin, 6 induced a marked increase of myocardial contractility, whereas 6 neither caused irregular frequency of oscillations nor cardiac cytotoxic effects under tested conditions. Structural modification on the butenolide moiety of uscharin showed a reduction of cardiac cytotoxicity and exhibited potential for use as an inotropic agent for the treatment of heart failure.

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Section: Resultsmentioning

confidence: 99%

Synthesis of 21‐Alkylidenes and 21‐Alkylol Analogues of Uscharin and Their Effects on Intracellular Calcium in Cardiac Cells

et al. 2019

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“…The configurations of double bonds on C-5 of compounds 9a～9o were cis-double bonds according to NMR and the previous works. [9,10] Among of synthetic compounds, compound 9l showed potent anticancer effect in gastric cancer MGC803 and less cytotoxicity in normal gastric epithelial cell line (GES1). Compound 9l has a 4-isopropyl phenyl group in its structure.…”

Section: Chemistrymentioning

confidence: 99%

Design and Synthesis of Novel Butenolide Derivatives and Inducing Apoptosis in Gastric Cancer Cells

Xu¹,

Li²,

Dong³

et al. 2020

Chin. J. Org. Chem.

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A new method of preparation for natural product Uncinine was reported. According to the method, a series of novel butenolides derivatives were designed and synthesized based on the natural product Uncinine. Most of the synthetic compounds showed significant anti proliferation activity against MGC-803. Among of them, (Z)-5-(4-(tert-butyl)benzylidene)-3-(morpholinomethyl)furan-2(5H)-one (9l) showed potent anticancer effect with IC 50 of 2.9 μmol/L in gastric cancer cell MGC803 and showed good selectivity to gastric cancer cells MGC803, HGC27, SGC7901 and less cytotoxicity in normal gastric epithelial cell line (GES1). The research on the molecular level suggests that the mechanism of compound 9l inducing apoptosis in gastric cancer cells is partially dependent on activation of caspase-9/3.

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γ-Benzylidene digoxin derivatives synthesis and molecular modeling: Evaluation of anticancer and the Na,K-ATPase activity effect

Alves

Paixão

Ferreira

et al. 2015

Bioorganic & Medicinal Chemistry

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Cardiotonic steroids (CS), natural compounds with traditional use in cardiology, have been recently suggested to exert potent anticancer effects. However, the repertoire of molecules with Na,K-ATPase activity and anticancer properties is limited. This paper describes the synthesis of 6 new digoxin derivatives substituted (on the C17-butenolide) with γ-benzylidene group and their cytotoxic effect on human fibroblast (WI-26 VA4) and cancer (HeLa and RKO) cell lines as well as their effect on Na,K-ATPase activity and expression. As digoxin, compound BD-4 was almost 100-fold more potent than the other derivatives for cytotoxicity with the three types of cells used and was also the only one able to fully inhibit the Na,K-ATPase of HeLa cells after 24h treatment. No change in the Na,K-ATPase α1 isoform protein expression was detected. On the other hand it was 30-40 fold less potent for direct Na,K-ATPase inhibition, when compared to the most potent derivatives, BD-1 and BD-3, and digoxin. The data presented here demonstrated that the anticancer effect of digoxin derivatives substituted with γ-benzylidene were not related with their inhibition of Na,K-ATPase activity or alteration of its expression, suggesting that this classical molecular mechanism of CS is not involved in the cytotoxic effect of our derivatives.

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Digoxin derivatives substituted by alkylidene at the butenolide part

Cited by 9 publications

References 11 publications

Synthesis of 21‐Alkylidenes and 21‐Alkylol Analogues of Uscharin and Their Effects on Intracellular Calcium in Cardiac Cells

Synthesis of 21‐Alkylidenes and 21‐Alkylol Analogues of Uscharin and Their Effects on Intracellular Calcium in Cardiac Cells

Design and Synthesis of Novel Butenolide Derivatives and Inducing Apoptosis in Gastric Cancer Cells

γ-Benzylidene digoxin derivatives synthesis and molecular modeling: Evaluation of anticancer and the Na,K-ATPase activity effect

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