SrasV1, Main, Curation, bibRecord, 004196

Pyridine N-oxide derivatives are inhibitory to the human SARS and feline infectious peritonitis coronavirus in cell culture

Identifieur interne : 004196 ( Main/Curation ); précédent : 004195; suivant : 004197

Pyridine N-oxide derivatives are inhibitory to the human SARS and feline infectious peritonitis coronavirus in cell culture

Auteurs : Jan Balzarini [Belgique] ; Els Keyaerts [Belgique] ; Leen Vijgen [Belgique] ; Frank Vandermeer [Pays-Bas] ; Miguel Stevens [Belgique] ; Erik De Clercq [Belgique] ; Herman Egberink [Pays-Bas] ; Marc Van Ranst [Belgique]

Source :

Journal of Antimicrobial Chemotherapy [ 0305-7453 ] ; 2005.

RBID : ISTEX:204CE38B08442996116884669633748144B69C3A

Descripteurs français

KwdFr :
- Animaux, Antiviraux (), Antiviraux (pharmacologie), Cellules cultivées, Chats, Coronavirus félin (), Humains, Pyridines (), Pyridines (pharmacologie), Relation structure-activité, Structure moléculaire, Virus du SRAS ().
MESH :
- pharmacologie : Antiviraux, Pyridines.
- Animaux, Antiviraux, Cellules cultivées, Chats, Coronavirus félin, Humains, Pyridines, Relation structure-activité, Structure moléculaire, Virus du SRAS.
Pascal (Inist)
- Coronavirus, Culture cellulaire, Homme, In vitro, Pyridine dérivé, Péritonite infectieuse féline, Syndrome respiratoire aigu sévère.
Wicri :
- topic : Homme.

English descriptors

KwdEn :
- Animals, Antiviral Agents (chemistry), Antiviral Agents (pharmacology), Cats, Cell culture, Cells, Cultured, Coronavirus, Coronavirus, Feline (drug effects), Feline infectious peritonitis, Human, Humans, In vitro, Molecular Structure, Pyridine derivatives, Pyridines (chemistry), Pyridines (pharmacology), SARS Virus (drug effects), Severe acute respiratory syndrome, Structure-Activity Relationship.
MESH :
- chemical , chemistry : Antiviral Agents, Pyridines.
- chemical , pharmacology : Antiviral Agents, Pyridines.
- drug effects : Coronavirus, Feline, SARS Virus.
- Animals, Cats, Cells, Cultured, Humans, Molecular Structure, Structure-Activity Relationship.

Abstract

Objectives: Evaluation of a wide variety of pyridine N-oxide derivatives on their inhibitory activity against feline coronavirus (FIPV strain) and human SARS-CoV (Frankfurt strain-1) in cell culture. Methods: FIPV and SARS-CoV were exposed to confluent Crandel feline kidney (CRFK) and simian kidney (Vero) cell cultures in the presence of serial concentrations of the test compounds. The anti-cytopathic activity of the pyridine N-oxide derivatives was monitored by spectrophotometric analysis. Results and conclusions: A wide variety of pyridine N-oxide derivatives have been found to be inhibitory against feline coronavirus (FIPV strain) and human SARS-CoV (Frankfurt strain-1) in CRFK and simian kidney (Vero) cell cultures, respectively. The oxide part on the pyridine moiety proved indispensable for anti-coronavirus activity. The potency and virus specificity of the pyridine N-oxide derivatives varied depending the nature and specific location of substituents (i.e. alkyl, halogeno, nitro, etc.) on the different parts of the molecule. The most selective compounds were active in the higher microgram per litre range, being non-toxic at 50–100 mg/L. There was a poor structure-antiviral activity relationship (SAR) for the pyridine N-oxide derivatives against Fe-CoV and SARS-CoV. One of the most active and selective compounds was shown to inhibit Fe-CoV replication at the transcriptional level.

Url:

DOI: 10.1093/jac/dki481

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ISTEX:204CE38B08442996116884669633748144B69C3A

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<term>Cell culture</term>
<term>Cells, Cultured</term>
<term>Coronavirus</term>
<term>Coronavirus, Feline (drug effects)</term>
<term>Feline infectious peritonitis</term>
<term>Human</term>
<term>Humans</term>
<term>In vitro</term>
<term>Molecular Structure</term>
<term>Pyridine derivatives</term>
<term>Pyridines (chemistry)</term>
<term>Pyridines (pharmacology)</term>
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<term>Antiviraux ()</term>
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<term>Humains</term>
<term>Pyridines ()</term>
<term>Pyridines (pharmacologie)</term>
<term>Relation structure-activité</term>
<term>Structure moléculaire</term>
<term>Virus du SRAS ()</term>
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<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antiviral Agents</term>
<term>Pyridines</term>
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<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term>
<term>Pyridines</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Coronavirus, Feline</term>
<term>SARS Virus</term>
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<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antiviraux</term>
<term>Pyridines</term>
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<term>Cats</term>
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<term>Chats</term>
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<term>Humains</term>
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<front><div type="abstract" xml:lang="en">Objectives: Evaluation of a wide variety of pyridine N-oxide derivatives on their inhibitory activity against feline coronavirus (FIPV strain) and human SARS-CoV (Frankfurt strain-1) in cell culture. Methods: FIPV and SARS-CoV were exposed to confluent Crandel feline kidney (CRFK) and simian kidney (Vero) cell cultures in the presence of serial concentrations of the test compounds. The anti-cytopathic activity of the pyridine N-oxide derivatives was monitored by spectrophotometric analysis. Results and conclusions: A wide variety of pyridine N-oxide derivatives have been found to be inhibitory against feline coronavirus (FIPV strain) and human SARS-CoV (Frankfurt strain-1) in CRFK and simian kidney (Vero) cell cultures, respectively. The oxide part on the pyridine moiety proved indispensable for anti-coronavirus activity. The potency and virus specificity of the pyridine N-oxide derivatives varied depending the nature and specific location of substituents (i.e. alkyl, halogeno, nitro, etc.) on the different parts of the molecule. The most selective compounds were active in the higher microgram per litre range, being non-toxic at 50–100 mg/L. There was a poor structure-antiviral activity relationship (SAR) for the pyridine N-oxide derivatives against Fe-CoV and SARS-CoV. One of the most active and selective compounds was shown to inhibit Fe-CoV replication at the transcriptional level.</div>
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<front><div type="abstract" xml:lang="en">Objectives: Evaluation of a wide variety of pyridine N-oxide derivatives on their inhibitory activity against feline coronavirus (FIPV strain) and human SARS-CoV (Frankfurt strain-1) in cell culture. Methods: FIPV and SARS-CoV were exposed to confluent Crandel feline kidney (CRFK) and simian kidney (Vero) cell cultures in the presence of serial concentrations of the test compounds. The anti-cytopathic activity of the pyridine N-oxide derivatives was monitored by spectrophotometric analysis. Results and conclusions: A wide variety of pyridine N-oxide derivatives have been found to be inhibitory against feline coronavirus (FIPV strain) and human SARS-CoV (Frankfurt strain-1) in CRFK and simian kidney (Vero) cell cultures, respectively. The oxide part on the pyridine moiety proved indispensable for anti-coronavirus activity. The potency and virus specificity of the pyridine N-oxide derivatives varied depending the nature and specific location of substituents (i.e. alkyl, halogeno, nitro, etc.) on the different parts of the molecule. The most selective compounds were active in the higher microgram per litre range, being non-toxic at 50-100 mg/L. There was a poor structure-antiviral activity relationship (SAR) for the pyridine N-oxide derivatives against Fe-CoV and SARS-CoV. One of the most active and selective compounds was shown to inhibit Fe-CoV replication at the transcriptional level.</div>
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<front><div type="abstract" xml:lang="en">Objectives: Evaluation of a wide variety of pyridine N-oxide derivatives on their inhibitory activity against feline coronavirus (FIPV strain) and human SARS-CoV (Frankfurt strain-1) in cell culture. Methods: FIPV and SARS-CoV were exposed to confluent Crandel feline kidney (CRFK) and simian kidney (Vero) cell cultures in the presence of serial concentrations of the test compounds. The anti-cytopathic activity of the pyridine N-oxide derivatives was monitored by spectrophotometric analysis. Results and conclusions: A wide variety of pyridine N-oxide derivatives have been found to be inhibitory against feline coronavirus (FIPV strain) and human SARS-CoV (Frankfurt strain-1) in CRFK and simian kidney (Vero) cell cultures, respectively. The oxide part on the pyridine moiety proved indispensable for anti-coronavirus activity. The potency and virus specificity of the pyridine N-oxide derivatives varied depending the nature and specific location of substituents (i.e. alkyl, halogeno, nitro, etc.) on the different parts of the molecule. The most selective compounds were active in the higher microgram per litre range, being non-toxic at 50–100 mg/L. There was a poor structure-antiviral activity relationship (SAR) for the pyridine N-oxide derivatives against Fe-CoV and SARS-CoV. One of the most active and selective compounds was shown to inhibit Fe-CoV replication at the transcriptional level.</div>
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Pyridine N-oxide derivatives are inhibitory to the human SARS and feline infectious peritonitis coronavirus in cell culture

Pyridine N-oxide derivatives are inhibitory to the human SARS and feline infectious peritonitis coronavirus in cell culture

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