Probing the Effects of Pyrimidine Functional Group Switches on Acyclic Fleximer Analogues for Antiviral Activity
Identifieur interne : 000421 ( Main/Exploration ); précédent : 000420; suivant : 000422Probing the Effects of Pyrimidine Functional Group Switches on Acyclic Fleximer Analogues for Antiviral Activity
Auteurs : Mary K. Yates [États-Unis] ; Payel Chatterjee [États-Unis] ; Mike Flint [États-Unis] ; Yafet Arefeayne [États-Unis] ; Damjan Makuc [Slovénie] ; Janez Plavec [Slovénie] ; Christina F. Spiropoulou [États-Unis] ; Katherine L. Seley-Radtke [États-Unis]Source :
- Molecules [ 1420-3049 ] ; 2019.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- Antiviral Agents (chemistry), Antiviral Agents (pharmacology), Cell Line, Tumor, Ebolavirus (drug effects), Humans, Indicators and Reagents, Lipids (chemistry), Molecular Conformation, Proton Magnetic Resonance Spectroscopy, Pyrimidines (chemistry), Pyrimidines (pharmacology), Structure-Activity Relationship.
- MESH :
- chemical , chemistry : Antiviral Agents, Lipids, Pyrimidines.
- chemical , pharmacology : Antiviral Agents, Pyrimidines.
- drug effects : Ebolavirus.
- Cell Line, Tumor, Humans, Indicators and Reagents, Molecular Conformation, Proton Magnetic Resonance Spectroscopy, Structure-Activity Relationship.
Abstract
Due to their ability to inhibit viral DNA or RNA replication, nucleoside analogues have been used for decades as potent antiviral therapeutics. However, one of the major limitations of nucleoside analogues is the development of antiviral resistance. In that regard, flexible nucleoside analogues known as “fleximers” have garnered attention over the years due to their ability to survey different amino acids in enzyme binding sites, thus overcoming the potential development of antiviral resistance. Acyclic fleximers have previously demonstrated antiviral activity against numerous viruses including Middle East Respiratory Syndrome coronavirus (MERS-CoV), Ebola virus (EBOV), and, most recently, flaviviruses such as Dengue (DENV) and Yellow Fever Virus (YFV). Due to these interesting results, a Structure Activity Relationship (SAR) study was pursued in order to analyze the effect of the pyrimidine functional group and acyl protecting group on antiviral activity, cytotoxicity, and conformation. The results of those studies are presented herein.
Url:
DOI: 10.3390/molecules24173184
PubMed: 31480658
PubMed Central: 6749450
Affiliations:
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Le document en format XML
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiviral Agents (chemistry)</term>
<term>Antiviral Agents (pharmacology)</term>
<term>Cell Line, Tumor</term>
<term>Ebolavirus (drug effects)</term>
<term>Humans</term>
<term>Indicators and Reagents</term>
<term>Lipids (chemistry)</term>
<term>Molecular Conformation</term>
<term>Proton Magnetic Resonance Spectroscopy</term>
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<term>Pyrimidines (pharmacology)</term>
<term>Structure-Activity Relationship</term>
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<term>Antiviraux (pharmacologie)</term>
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<term>Ebolavirus ()</term>
<term>Humains</term>
<term>Indicateurs et réactifs</term>
<term>Lignée cellulaire tumorale</term>
<term>Lipides ()</term>
<term>Pyrimidines ()</term>
<term>Pyrimidines (pharmacologie)</term>
<term>Relation structure-activité</term>
<term>Spectroscopie par résonance magnétique du proton</term>
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<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antiviral Agents</term>
<term>Lipids</term>
<term>Pyrimidines</term>
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<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term>
<term>Pyrimidines</term>
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<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antiviraux</term>
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<term>Indicators and Reagents</term>
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<term>Proton Magnetic Resonance Spectroscopy</term>
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<front><div type="abstract" xml:lang="en"><p>Due to their ability to inhibit viral DNA or RNA replication, nucleoside analogues have been used for decades as potent antiviral therapeutics. However, one of the major limitations of nucleoside analogues is the development of antiviral resistance. In that regard, flexible nucleoside analogues known as “fleximers” have garnered attention over the years due to their ability to survey different amino acids in enzyme binding sites, thus overcoming the potential development of antiviral resistance. Acyclic fleximers have previously demonstrated antiviral activity against numerous viruses including Middle East Respiratory Syndrome coronavirus (MERS-CoV), Ebola virus (EBOV), and, most recently, flaviviruses such as Dengue (DENV) and Yellow Fever Virus (YFV). Due to these interesting results, a Structure Activity Relationship (SAR) study was pursued in order to analyze the effect of the pyrimidine functional group and acyl protecting group on antiviral activity, cytotoxicity, and conformation. The results of those studies are presented herein.</p>
</div>
</front>
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<affiliations><list><country><li>Slovénie</li>
<li>États-Unis</li>
</country>
<region><li>Géorgie (États-Unis)</li>
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</region>
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