Structure-activity relationships of 3-O-β-chacotriosyl oleanic acid derivatives as entry inhibitors for highly pathogenic H5N1 influenza virus.
Identifieur interne : 002E22 ( Ncbi/Merge ); précédent : 002E21; suivant : 002E23Structure-activity relationships of 3-O-β-chacotriosyl oleanic acid derivatives as entry inhibitors for highly pathogenic H5N1 influenza virus.
Auteurs : Sumei Li [République populaire de Chine] ; Xiuhua Jia [République populaire de Chine] ; Xintian Shen [République populaire de Chine] ; Zhuwen Wei [République populaire de Chine] ; Zhiyan Jiang [République populaire de Chine] ; Yixian Liao [République populaire de Chine] ; Yiming Guo [République populaire de Chine] ; Xiaojun Zheng [République populaire de Chine] ; Guohua Zhong [République populaire de Chine] ; Gaopeng Song [République populaire de Chine]Source :
- Bioorganic & medicinal chemistry [ 1464-3391 ] ; 2017.
Descripteurs français
- KwdFr :
- Acide oléanolique (), Acide oléanolique (pharmacologie), Acide oléanolique (synthèse chimique), Animaux, Antiviraux (), Antiviraux (pharmacologie), Antiviraux (synthèse chimique), Cellules rénales canines Madin-Darby (), Cellules rénales canines Madin-Darby (virologie), Chiens, Relation dose-effet des médicaments, Relation structure-activité, Sous-type H5N1 du virus de la grippe A (), Structure moléculaire, Tests de sensibilité microbienne.
- MESH :
- pharmacologie : Acide oléanolique, Antiviraux.
- synthèse chimique : Acide oléanolique, Antiviraux.
- virologie : Cellules rénales canines Madin-Darby.
- Acide oléanolique, Animaux, Antiviraux, Cellules rénales canines Madin-Darby, Chiens, Relation dose-effet des médicaments, Relation structure-activité, Sous-type H5N1 du virus de la grippe A, Structure moléculaire, Tests de sensibilité microbienne.
English descriptors
- KwdEn :
- Animals, Antiviral Agents (chemical synthesis), Antiviral Agents (chemistry), Antiviral Agents (pharmacology), Dogs, Dose-Response Relationship, Drug, Influenza A Virus, H5N1 Subtype (drug effects), Madin Darby Canine Kidney Cells (drug effects), Madin Darby Canine Kidney Cells (virology), Microbial Sensitivity Tests, Molecular Structure, Oleanolic Acid (chemical synthesis), Oleanolic Acid (chemistry), Oleanolic Acid (pharmacology), Structure-Activity Relationship.
- MESH :
- chemical , chemical synthesis : Antiviral Agents, Oleanolic Acid.
- chemical , chemistry : Antiviral Agents, Oleanolic Acid.
- chemical , pharmacology : Antiviral Agents, Oleanolic Acid.
- drug effects : Influenza A Virus, H5N1 Subtype, Madin Darby Canine Kidney Cells.
- virology : Madin Darby Canine Kidney Cells.
- Animals, Dogs, Dose-Response Relationship, Drug, Microbial Sensitivity Tests, Molecular Structure, Structure-Activity Relationship.
Abstract
Highly pathogenic H5N1 virus (H5N1) entry is a key target for the development of novel anti-influenza agents with new mechanisms of action. In our continuing efforts to identify novel potential anti-H5N1 entry inhibitors, a series of 3-O-β-chacotriosyl oleanolic acid analogs have been designed, synthesized and evaluated as H5N1 entry inhibitors based on two small molecule inhibitors 1 and 2 previously discovered by us. The anti-H5N1 entry activities were determined based on HA/HIV and VSVG/HIV entry assays. Compound 15 displayed the most promising anti-H5N1 entry activities with average IC50 values of 4.05μM and good selective index (22.9). Detailed structure-activity relationships (SARs) studies suggested that either the introduction of an additional oxo group to position 11 at OA or alteration of the C-3 configuration of OA from 3β- to 3α-forms can significantly enhance the selective index while maintaining their antiviral activities in vitro. Molecular simulation analysis confirmed that the compounds exert their inhibitory activity through binding tightly to hemagglutinin (HA2) protein near the fusion peptide and prevent virus entry.
DOI: 10.1016/j.bmc.2017.06.025
PubMed: 28651913
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pubmed:28651913Le document en format XML
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<term>Madin Darby Canine Kidney Cells (virology)</term>
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<front><div type="abstract" xml:lang="en">Highly pathogenic H5N1 virus (H5N1) entry is a key target for the development of novel anti-influenza agents with new mechanisms of action. In our continuing efforts to identify novel potential anti-H5N1 entry inhibitors, a series of 3-O-β-chacotriosyl oleanolic acid analogs have been designed, synthesized and evaluated as H5N1 entry inhibitors based on two small molecule inhibitors 1 and 2 previously discovered by us. The anti-H5N1 entry activities were determined based on HA/HIV and VSVG/HIV entry assays. Compound 15 displayed the most promising anti-H5N1 entry activities with average IC<sub>50</sub>
values of 4.05μM and good selective index (22.9). Detailed structure-activity relationships (SARs) studies suggested that either the introduction of an additional oxo group to position 11 at OA or alteration of the C-3 configuration of OA from 3β- to 3α-forms can significantly enhance the selective index while maintaining their antiviral activities in vitro. Molecular simulation analysis confirmed that the compounds exert their inhibitory activity through binding tightly to hemagglutinin (HA2) protein near the fusion peptide and prevent virus entry.</div>
</front>
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<Abstract><AbstractText>Highly pathogenic H5N1 virus (H5N1) entry is a key target for the development of novel anti-influenza agents with new mechanisms of action. In our continuing efforts to identify novel potential anti-H5N1 entry inhibitors, a series of 3-O-β-chacotriosyl oleanolic acid analogs have been designed, synthesized and evaluated as H5N1 entry inhibitors based on two small molecule inhibitors 1 and 2 previously discovered by us. The anti-H5N1 entry activities were determined based on HA/HIV and VSVG/HIV entry assays. Compound 15 displayed the most promising anti-H5N1 entry activities with average IC<sub>50</sub>
values of 4.05μM and good selective index (22.9). Detailed structure-activity relationships (SARs) studies suggested that either the introduction of an additional oxo group to position 11 at OA or alteration of the C-3 configuration of OA from 3β- to 3α-forms can significantly enhance the selective index while maintaining their antiviral activities in vitro. Molecular simulation analysis confirmed that the compounds exert their inhibitory activity through binding tightly to hemagglutinin (HA2) protein near the fusion peptide and prevent virus entry.</AbstractText>
<CopyrightInformation>Copyright © 2017 Elsevier Ltd. All rights reserved.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Li</LastName>
<ForeName>Sumei</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Human Anatomy, School of Medicine, Jinan University, Guangzhou 510632, China.</Affiliation>
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<ForeName>Xiuhua</ForeName>
<Initials>X</Initials>
<AffiliationInfo><Affiliation>Department of Ophthalmology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.</Affiliation>
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<Author ValidYN="Y"><LastName>Shen</LastName>
<ForeName>Xintian</ForeName>
<Initials>X</Initials>
<AffiliationInfo><Affiliation>Department of Pharmacy, Maternal and Child Health Hospital of Bao'an District, Shenzhen 518133, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wei</LastName>
<ForeName>Zhuwen</ForeName>
<Initials>Z</Initials>
<AffiliationInfo><Affiliation>College of Materials and Energy, South China Agricultural University, Guangzhou 510642, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Jiang</LastName>
<ForeName>Zhiyan</ForeName>
<Initials>Z</Initials>
<AffiliationInfo><Affiliation>Key Laboratory of Natural Pesticide and Chemical Biology, Ministry of Education, and Lab of Insect Toxicology, South China Agricultural University, Guangzhou 510642, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Liao</LastName>
<ForeName>Yixian</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>College of Materials and Energy, South China Agricultural University, Guangzhou 510642, China.</Affiliation>
</AffiliationInfo>
</Author>
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<ForeName>Yiming</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>College of Materials and Energy, South China Agricultural University, Guangzhou 510642, China.</Affiliation>
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</Author>
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<ForeName>Xiaojun</ForeName>
<Initials>X</Initials>
<AffiliationInfo><Affiliation>College of Materials and Energy, South China Agricultural University, Guangzhou 510642, China.</Affiliation>
</AffiliationInfo>
</Author>
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<ForeName>Guohua</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>Key Laboratory of Natural Pesticide and Chemical Biology, Ministry of Education, and Lab of Insect Toxicology, South China Agricultural University, Guangzhou 510642, China. Electronic address: guohuazhong@scau.edu.cn.</Affiliation>
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<ForeName>Gaopeng</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>College of Materials and Energy, South China Agricultural University, Guangzhou 510642, China. Electronic address: vinsin1021@126.com.</Affiliation>
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<Language>eng</Language>
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<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
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<ArticleDate DateType="Electronic"><Year>2017</Year>
<Month>06</Month>
<Day>15</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>England</Country>
<MedlineTA>Bioorg Med Chem</MedlineTA>
<NlmUniqueID>9413298</NlmUniqueID>
<ISSNLinking>0968-0896</ISSNLinking>
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<NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance>
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<Chemical><RegistryNumber>6SMK8R7TGJ</RegistryNumber>
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<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
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<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
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<Keyword MajorTopicYN="Y">H5N1 entry inhibitors</Keyword>
<Keyword MajorTopicYN="Y">Structure-activity relationships</Keyword>
<Keyword MajorTopicYN="Y">Synthesis</Keyword>
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<Day>04</Day>
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<PubMedPubDate PubStatus="revised"><Year>2017</Year>
<Month>06</Month>
<Day>05</Day>
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<PubMedPubDate PubStatus="accepted"><Year>2017</Year>
<Month>06</Month>
<Day>13</Day>
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<Month>6</Month>
<Day>28</Day>
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<ArticleIdList><ArticleId IdType="pubmed">28651913</ArticleId>
<ArticleId IdType="pii">S0968-0896(17)30720-4</ArticleId>
<ArticleId IdType="doi">10.1016/j.bmc.2017.06.025</ArticleId>
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<affiliations><list><country><li>République populaire de Chine</li>
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<name sortKey="Guo, Yiming" sort="Guo, Yiming" uniqKey="Guo Y" first="Yiming" last="Guo">Yiming Guo</name>
<name sortKey="Jia, Xiuhua" sort="Jia, Xiuhua" uniqKey="Jia X" first="Xiuhua" last="Jia">Xiuhua Jia</name>
<name sortKey="Jiang, Zhiyan" sort="Jiang, Zhiyan" uniqKey="Jiang Z" first="Zhiyan" last="Jiang">Zhiyan Jiang</name>
<name sortKey="Liao, Yixian" sort="Liao, Yixian" uniqKey="Liao Y" first="Yixian" last="Liao">Yixian Liao</name>
<name sortKey="Shen, Xintian" sort="Shen, Xintian" uniqKey="Shen X" first="Xintian" last="Shen">Xintian Shen</name>
<name sortKey="Song, Gaopeng" sort="Song, Gaopeng" uniqKey="Song G" first="Gaopeng" last="Song">Gaopeng Song</name>
<name sortKey="Wei, Zhuwen" sort="Wei, Zhuwen" uniqKey="Wei Z" first="Zhuwen" last="Wei">Zhuwen Wei</name>
<name sortKey="Zheng, Xiaojun" sort="Zheng, Xiaojun" uniqKey="Zheng X" first="Xiaojun" last="Zheng">Xiaojun Zheng</name>
<name sortKey="Zhong, Guohua" sort="Zhong, Guohua" uniqKey="Zhong G" first="Guohua" last="Zhong">Guohua Zhong</name>
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