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Chalcones isolated from Angelica keiskei inhibit cysteine proteases of SARS-CoV.

Identifieur interne : 000E62 ( PubMed/Curation ); précédent : 000E61; suivant : 000E63

Chalcones isolated from Angelica keiskei inhibit cysteine proteases of SARS-CoV.

Auteurs : Ji-Young Park [Corée du Sud] ; Jin-A Ko [Corée du Sud] ; Dae Wook Kim ; Young Min Kim [Corée du Sud] ; Hyung-Jun Kwon [Corée du Sud] ; Hyung Jae Jeong [Corée du Sud] ; Cha Young Kim [Corée du Sud] ; Ki Hun Park ; Woo Song Lee [Corée du Sud] ; Young Bae Ryu [Corée du Sud]

Source :

RBID : pubmed:25683083

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English descriptors

Abstract

Two viral proteases of severe acute respiratory syndrome coronavirus (SARS-CoV), a chymotrypsin-like protease (3CL(pro)) and a papain-like protease (PL(pro)) are attractive targets for the development of anti-SARS drugs. In this study, nine alkylated chalcones (1-9) and four coumarins (10-13) were isolated from Angelica keiskei, and the inhibitory activities of these constituents against SARS-CoV proteases (3CL(pro) and PL(pro)) were determined (cell-free/based). Of the isolated alkylated chalcones, chalcone 6, containing the perhydroxyl group, exhibited the most potent 3CL(pro) and PL(pro) inhibitory activity with IC50 values of 11.4 and 1.2 µM. Our detailed protein-inhibitor mechanistic analysis of these species indicated that the chalcones exhibited competitive inhibition characteristics to the SARS-CoV 3CL(pro), whereas noncompetitive inhibition was observed with the SARS-CoV PL(pro).

DOI: 10.3109/14756366.2014.1003215
PubMed: 25683083

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Dae Wook Kim
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Ki Hun Park
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Le document en format XML

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<term>Antiviral Agents (isolation & purification)</term>
<term>Antiviral Agents (pharmacology)</term>
<term>Chalcones (chemistry)</term>
<term>Chalcones (isolation & purification)</term>
<term>Chalcones (pharmacology)</term>
<term>Cysteine Proteases (metabolism)</term>
<term>Cysteine Proteinase Inhibitors (chemistry)</term>
<term>Cysteine Proteinase Inhibitors (isolation & purification)</term>
<term>Cysteine Proteinase Inhibitors (pharmacology)</term>
<term>Dose-Response Relationship, Drug</term>
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<term>Antiviraux (pharmacologie)</term>
<term>Chalcones ()</term>
<term>Chalcones (isolement et purification)</term>
<term>Chalcones (pharmacologie)</term>
<term>Cysteine proteases (métabolisme)</term>
<term>Inhibiteurs de la cystéine protéinase ()</term>
<term>Inhibiteurs de la cystéine protéinase (isolement et purification)</term>
<term>Inhibiteurs de la cystéine protéinase (pharmacologie)</term>
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<div type="abstract" xml:lang="en">Two viral proteases of severe acute respiratory syndrome coronavirus (SARS-CoV), a chymotrypsin-like protease (3CL(pro)) and a papain-like protease (PL(pro)) are attractive targets for the development of anti-SARS drugs. In this study, nine alkylated chalcones (1-9) and four coumarins (10-13) were isolated from Angelica keiskei, and the inhibitory activities of these constituents against SARS-CoV proteases (3CL(pro) and PL(pro)) were determined (cell-free/based). Of the isolated alkylated chalcones, chalcone 6, containing the perhydroxyl group, exhibited the most potent 3CL(pro) and PL(pro) inhibitory activity with IC50 values of 11.4 and 1.2 µM. Our detailed protein-inhibitor mechanistic analysis of these species indicated that the chalcones exhibited competitive inhibition characteristics to the SARS-CoV 3CL(pro), whereas noncompetitive inhibition was observed with the SARS-CoV PL(pro). </div>
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<QualifierName UI="Q000302" MajorTopicYN="N">isolation & purification</QualifierName>
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<Keyword MajorTopicYN="N">3CLpro</Keyword>
<Keyword MajorTopicYN="N">Angelica keiskei</Keyword>
<Keyword MajorTopicYN="N">PLpro</Keyword>
<Keyword MajorTopicYN="N">SARS-CoV</Keyword>
<Keyword MajorTopicYN="N">chalcone</Keyword>
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<Day>17</Day>
<Hour>6</Hour>
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<Day>17</Day>
<Hour>6</Hour>
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<Year>2016</Year>
<Month>10</Month>
<Day>8</Day>
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<ArticleId IdType="doi">10.3109/14756366.2014.1003215</ArticleId>
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