Research Progress in Pharmacological Activities and Applications of Cardiotonic Steroids

Ren, Junwei; Gao, Xinyuan; Guo, Xi; Wang, Ning; Wang, Xin

doi:10.3389/fphar.2022.902459

Cited by 12 publications

(7 citation statements)

References 124 publications

(161 reference statements)

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“…164 The N1L antagonists are polyphenols with IC 50 values from 600 to 900 nM in the fluorescence polarization assay. The antiviral activity of ID29 (152) and ID31 (153) was further confirmed in the antiviral assay using the GFPexpressing recombinant VACV.…”

Section: Virucidal Compoundsmentioning

confidence: 75%

“…Deng et al screened a library of 2880 compounds against VACV and identified 13 hits, including steroid glycoside natural products digoxin ( 122 ), cimarin ( 123 ), neriifolin ( 124 ), ouabain ( 125 ), and lanatoside C ( 126 ); eukaryotic protein synthesis inhibitors cycloheximide ( 127 ), anisomycin ( 128 ), emetine ( 129 ), and cephaeline ( 130 ); mycophenolic acid ( 131 ), ancitabine ( 132 ), mitoxantrone ( 133 ), and lycorine ( 134 ) (Figure ). Digoxin ( 122 ) and ouabain ( 125 ) have been evaluated in clinical trials for various diseases …”

Section: Antivirals Against Orthopoxvirusesmentioning

confidence: 99%

“…Digoxin (122) and ouabain (125) have been evaluated in clinical trials for various diseases. 153 Mitoxantrone (133) had a unique mechanism of action by inhibiting late protein synthesis. Resistance selection identified three mitoxantrone (133)-resistant strains with either mutations or insertion in the vaccinia DNA ligase.…”

Section: Virucidal Compoundsmentioning

confidence: 99%

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An Overview of Antivirals against Monkeypox Virus and Other Orthopoxviruses

et al. 2023

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The current monkeypox outbreaks during the COVID-19 pandemic have reignited interest in orthopoxvirus antivirals. Monkeypox belongs to the Orthopoxvirus genus of the Poxviridae family, which also includes the variola virus, vaccinia virus, and cowpox virus. Two orally bioavailable drugs, tecovirimat and brincidofovir, have been approved for treating smallpox infections. Given their human safety profiles and in vivo antiviral efficacy in animal models, both drugs have also been recommended to treat monkeypox infection. To facilitate the development of additional orthopoxvirus antivirals, we summarize the antiviral activity, mechanism of action, and mechanism of resistance of orthopoxvirus antivirals. This perspective covers both direct-acting and host-targeting antivirals with an emphasis on drug candidates showing in vivo antiviral efficacy in animal models. We hope to speed the orthopoxvirus antiviral drug discovery by providing medicinal chemists with insights into prioritizing proper drug targets and hits for further development.

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Section: Virucidal Compoundsmentioning

confidence: 75%

Section: Antivirals Against Orthopoxvirusesmentioning

confidence: 99%

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An Overview of Antivirals against Monkeypox Virus and Other Orthopoxviruses

et al. 2023

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“…CTS are classified as endogenous or exogenous (cardiac glycoside) based on their source. Endogenous CTS functions in mammals as endogenous digitalis-like factors (135). Among the most extensively studied endogenous CTS are cardenolides (ouabain and digoxin) and bufadienolides (marinobufagenin, telocinobufagin, and 19-Norbufalin) (14, 136).…”

Section: Therapeutic Targetmentioning

confidence: 99%

“…Digitalis lanata and Digitalis purpurea are the primary sources of cardiac glycosides (134). Digitoxin, digoxin, lantoside C, and strophanthin K are clinical preparations in use (135).…”

Section: Therapeutic Targetmentioning

confidence: 99%

The Na+/K+-ATPase: A potential therapeutic target in cardiometabolic diseases

Obradović

Sudar-Milovanović²,

Gluvić³

et al. 2023

Front. Endocrinol.

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Cardiometabolic diseases (CMD) are a direct consequence of modern living and contribute to the development of multisystem diseases such as cardiovascular diseases and diabetes mellitus (DM). CMD has reached epidemic proportions worldwide. A sodium pump (Na+/K+-ATPase) is found in most eukaryotic cells’ membrane and controls many essential cellular functions directly or indirectly. This ion transporter and its isoforms are important in the pathogenesis of some pathological processes, including CMD. The structure and function of Na+/K+-ATPase, its expression and distribution in tissues, and its interactions with known ligands such as cardiotonic steroids and other suspected endogenous regulators are discussed in this review. In addition, we reviewed recent literature data related to the involvement of Na+/K+-ATPase activity dysfunction in CMD, focusing on the Na+/K+-ATPase as a potential therapeutic target in CMD.

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The mechanistic role of cardiac glycosides in DNA damage response and repair signaling

Ainembabazi

Zhang

Turchi

2023

Cell. Mol. Life Sci.

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Cardiac glycosides (CGs) are a class of bioactive organic compounds well-known for their application in treating heart disease despite a narrow therapeutic window. Considerable evidence has demonstrated the potential to repurpose CGs for cancer treatment. Chemical modification of these CGs has been utilized in attempts to increase their anti-cancer properties; however, this has met limited success as their mechanism of action is still speculative. Recent studies have identified the DNA damage response (DDR) pathway as a target of CGs. DDR serves to coordinate numerous cellular pathways to initiate cell cycle arrest, promote DNA repair, regulate replication fork firing and protection, or induce apoptosis to avoid the survival of cells with DNA damage or cells carrying mutations. Understanding the modus operandi of cardiac glycosides will provide critical information to better address improvements in potency, reduced toxicity, and the potential to overcome drug resistance. This review summarizes recent scientific findings of the molecular mechanisms of cardiac glycosides affecting the DDR signaling pathway in cancer therapeutics from 2010 to 2022. We focus on the structural and functional differences of CGs toward identifying the critical features for DDR targeting of these agents.

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Research Progress in Pharmacological Activities and Applications of Cardiotonic Steroids

Cited by 12 publications

References 124 publications

An Overview of Antivirals against Monkeypox Virus and Other Orthopoxviruses

An Overview of Antivirals against Monkeypox Virus and Other Orthopoxviruses

The Na+/K+-ATPase: A potential therapeutic target in cardiometabolic diseases

The mechanistic role of cardiac glycosides in DNA damage response and repair signaling

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