Structure-activity relationships of 3-O-β-chacotriosyl ursolic acid derivatives as novel H5N1 entry inhibitors.
Identifieur interne : 000E53 ( PubMed/Corpus ); précédent : 000E52; suivant : 000E54Structure-activity relationships of 3-O-β-chacotriosyl ursolic acid derivatives as novel H5N1 entry inhibitors.
Auteurs : Gaopeng Song ; Xintian Shen ; Sumei Li ; Yibin Li ; Yunpeng Liu ; Yushan Zheng ; Ruheng Lin ; Jihong Fan ; Hanming Ye ; Shuwen LiuSource :
- European journal of medicinal chemistry [ 1768-3254 ] ; 2015.
English descriptors
- KwdEn :
- Animals, Antiviral Agents (chemistry), Antiviral Agents (pharmacology), Dogs, HEK293 Cells, Humans, Influenza A Virus, H5N1 Subtype (drug effects), Influenza A Virus, H5N1 Subtype (physiology), Madin Darby Canine Kidney Cells, Structure-Activity Relationship, Triterpenes (chemistry), Triterpenes (pharmacology), Tropanes (chemistry), Virus Internalization (drug effects).
- MESH :
- chemical , chemistry : Antiviral Agents, Triterpenes, Tropanes.
- chemical , pharmacology : Antiviral Agents, Triterpenes.
- drug effects : Influenza A Virus, H5N1 Subtype, Virus Internalization.
- physiology : Influenza A Virus, H5N1 Subtype.
- Animals, Dogs, HEK293 Cells, Humans, Madin Darby Canine Kidney Cells, Structure-Activity Relationship.
Abstract
A series of methyl ursolate 3-O-β-chacotrioside analogs have been designed, synthesized and evaluated as H5N1 entry inhibitors based on a small molecule inhibitor saponin 3 previously discovered by us. Detailed structure-activity relationships (SARs) studies on the aglycone of compound 3 indicated that both the type of pentacyclic triterpene and the subtle modification of ursolic acid as an aglycon had key influences on the antiviral activity. These results suggested that either the introduction of a disubstituted amide structure at the 17-COOH of ursolic acid or alteration of the C-3 configuration of ursolic acid from 3β-to 3α-forms was helpful to significantly improve the selective index while keeping their antiviral activities.
DOI: 10.1016/j.ejmech.2015.02.029
PubMed: 25728024
Links to Exploration step
pubmed:25728024Le document en format XML
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Electronic address: vinsin1021@126.com.</nlm:affiliation></affiliation></author><author><name sortKey="Shen, Xintian" sort="Shen, Xintian" uniqKey="Shen X" first="Xintian" last="Shen">Xintian Shen</name><affiliation><nlm:affiliation>School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.</nlm:affiliation></affiliation></author><author><name sortKey="Li, Sumei" sort="Li, Sumei" uniqKey="Li S" first="Sumei" last="Li">Sumei Li</name><affiliation><nlm:affiliation>Department of Human Anatomy, School of Medicine, Jinan University, Guangzhou, 510632, China.</nlm:affiliation></affiliation></author><author><name sortKey="Li, Yibin" sort="Li, Yibin" uniqKey="Li Y" first="Yibin" last="Li">Yibin Li</name><affiliation><nlm:affiliation>College of Resources and Environment, South China Agricultural University, Guangzhou, 510642, China.</nlm:affiliation></affiliation></author><author><name sortKey="Liu, Yunpeng" sort="Liu, Yunpeng" uniqKey="Liu Y" first="Yunpeng" last="Liu">Yunpeng Liu</name><affiliation><nlm:affiliation>Center for Diagnostics and Therapeutics, Department of Chemistry, Georgia State University, Atlanta, GA, 30303, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Zheng, Yushan" sort="Zheng, Yushan" uniqKey="Zheng Y" first="Yushan" last="Zheng">Yushan Zheng</name><affiliation><nlm:affiliation>College of Resources and Environment, South China Agricultural University, Guangzhou, 510642, China.</nlm:affiliation></affiliation></author><author><name sortKey="Lin, Ruheng" sort="Lin, Ruheng" uniqKey="Lin R" first="Ruheng" last="Lin">Ruheng Lin</name><affiliation><nlm:affiliation>College of Resources and Environment, South China Agricultural University, Guangzhou, 510642, China.</nlm:affiliation></affiliation></author><author><name sortKey="Fan, Jihong" sort="Fan, Jihong" uniqKey="Fan J" first="Jihong" last="Fan">Jihong Fan</name><affiliation><nlm:affiliation>College of Resources and Environment, South China Agricultural University, Guangzhou, 510642, China.</nlm:affiliation></affiliation></author><author><name sortKey="Ye, Hanming" sort="Ye, Hanming" uniqKey="Ye H" first="Hanming" last="Ye">Hanming Ye</name><affiliation><nlm:affiliation>College of Resources and Environment, South China Agricultural University, Guangzhou, 510642, China.</nlm:affiliation></affiliation></author><author><name sortKey="Liu, Shuwen" sort="Liu, Shuwen" uniqKey="Liu S" first="Shuwen" last="Liu">Shuwen Liu</name><affiliation><nlm:affiliation>School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. 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Electronic address: vinsin1021@126.com.</nlm:affiliation></affiliation></author><author><name sortKey="Shen, Xintian" sort="Shen, Xintian" uniqKey="Shen X" first="Xintian" last="Shen">Xintian Shen</name><affiliation><nlm:affiliation>School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.</nlm:affiliation></affiliation></author><author><name sortKey="Li, Sumei" sort="Li, Sumei" uniqKey="Li S" first="Sumei" last="Li">Sumei Li</name><affiliation><nlm:affiliation>Department of Human Anatomy, School of Medicine, Jinan University, Guangzhou, 510632, China.</nlm:affiliation></affiliation></author><author><name sortKey="Li, Yibin" sort="Li, Yibin" uniqKey="Li Y" first="Yibin" last="Li">Yibin Li</name><affiliation><nlm:affiliation>College of Resources and Environment, South China Agricultural University, Guangzhou, 510642, China.</nlm:affiliation></affiliation></author><author><name sortKey="Liu, Yunpeng" sort="Liu, Yunpeng" uniqKey="Liu Y" first="Yunpeng" last="Liu">Yunpeng Liu</name><affiliation><nlm:affiliation>Center for Diagnostics and Therapeutics, Department of Chemistry, Georgia State University, Atlanta, GA, 30303, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Zheng, Yushan" sort="Zheng, Yushan" uniqKey="Zheng Y" first="Yushan" last="Zheng">Yushan Zheng</name><affiliation><nlm:affiliation>College of Resources and Environment, South China Agricultural University, Guangzhou, 510642, China.</nlm:affiliation></affiliation></author><author><name sortKey="Lin, Ruheng" sort="Lin, Ruheng" uniqKey="Lin R" first="Ruheng" last="Lin">Ruheng Lin</name><affiliation><nlm:affiliation>College of Resources and Environment, South China Agricultural University, Guangzhou, 510642, China.</nlm:affiliation></affiliation></author><author><name sortKey="Fan, Jihong" sort="Fan, Jihong" uniqKey="Fan J" first="Jihong" last="Fan">Jihong Fan</name><affiliation><nlm:affiliation>College of Resources and Environment, South China Agricultural University, Guangzhou, 510642, China.</nlm:affiliation></affiliation></author><author><name sortKey="Ye, Hanming" sort="Ye, Hanming" uniqKey="Ye H" first="Hanming" last="Ye">Hanming Ye</name><affiliation><nlm:affiliation>College of Resources and Environment, South China Agricultural University, Guangzhou, 510642, China.</nlm:affiliation></affiliation></author><author><name sortKey="Liu, Shuwen" sort="Liu, Shuwen" uniqKey="Liu S" first="Shuwen" last="Liu">Shuwen Liu</name><affiliation><nlm:affiliation>School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. Electronic address: liusw@smu.edu.cn.</nlm:affiliation></affiliation></author></analytic><series><title level="j">European journal of medicinal chemistry</title><idno type="eISSN">1768-3254</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antiviral Agents (chemistry)</term><term>Antiviral Agents (pharmacology)</term><term>Dogs</term><term>HEK293 Cells</term><term>Humans</term><term>Influenza A Virus, H5N1 Subtype (drug effects)</term><term>Influenza A Virus, H5N1 Subtype (physiology)</term><term>Madin Darby Canine Kidney Cells</term><term>Structure-Activity Relationship</term><term>Triterpenes (chemistry)</term><term>Triterpenes (pharmacology)</term><term>Tropanes (chemistry)</term><term>Virus Internalization (drug effects)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antiviral Agents</term><term>Triterpenes</term><term>Tropanes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term><term>Triterpenes</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Influenza A Virus, H5N1 Subtype</term><term>Virus Internalization</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Influenza A Virus, H5N1 Subtype</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Dogs</term><term>HEK293 Cells</term><term>Humans</term><term>Madin Darby Canine Kidney Cells</term><term>Structure-Activity Relationship</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">A series of methyl ursolate 3-O-β-chacotrioside analogs have been designed, synthesized and evaluated as H5N1 entry inhibitors based on a small molecule inhibitor saponin 3 previously discovered by us. Detailed structure-activity relationships (SARs) studies on the aglycone of compound 3 indicated that both the type of pentacyclic triterpene and the subtle modification of ursolic acid as an aglycon had key influences on the antiviral activity. These results suggested that either the introduction of a disubstituted amide structure at the 17-COOH of ursolic acid or alteration of the C-3 configuration of ursolic acid from 3β-to 3α-forms was helpful to significantly improve the selective index while keeping their antiviral activities. </div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25728024</PMID><DateCompleted><Year>2015</Year><Month>12</Month><Day>21</Day></DateCompleted><DateRevised><Year>2015</Year><Month>03</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1768-3254</ISSN><JournalIssue CitedMedium="Internet"><Volume>93</Volume><PubDate><Year>2015</Year><Month>Mar</Month><Day>26</Day></PubDate></JournalIssue><Title>European journal of medicinal chemistry</Title><ISOAbbreviation>Eur J Med Chem</ISOAbbreviation></Journal><ArticleTitle>Structure-activity relationships of 3-O-β-chacotriosyl ursolic acid derivatives as novel H5N1 entry inhibitors.</ArticleTitle><Pagination><MedlinePgn>431-42</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.ejmech.2015.02.029</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S0223-5234(15)00125-7</ELocationID><Abstract><AbstractText>A series of methyl ursolate 3-O-β-chacotrioside analogs have been designed, synthesized and evaluated as H5N1 entry inhibitors based on a small molecule inhibitor saponin 3 previously discovered by us. Detailed structure-activity relationships (SARs) studies on the aglycone of compound 3 indicated that both the type of pentacyclic triterpene and the subtle modification of ursolic acid as an aglycon had key influences on the antiviral activity. These results suggested that either the introduction of a disubstituted amide structure at the 17-COOH of ursolic acid or alteration of the C-3 configuration of ursolic acid from 3β-to 3α-forms was helpful to significantly improve the selective index while keeping their antiviral activities. </AbstractText><CopyrightInformation>Copyright © 2015 Elsevier Masson SAS. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Song</LastName><ForeName>Gaopeng</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>College of Resources and Environment, South China Agricultural University, Guangzhou, 510642, China. Electronic address: vinsin1021@126.com.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shen</LastName><ForeName>Xintian</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.</Affiliation></AffiliationInfo></Author><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></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Yibin</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>College of Resources and Environment, South China Agricultural University, Guangzhou, 510642, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Yunpeng</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Center for Diagnostics and Therapeutics, Department of Chemistry, Georgia State University, Atlanta, GA, 30303, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zheng</LastName><ForeName>Yushan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>College of Resources and Environment, South China Agricultural University, Guangzhou, 510642, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lin</LastName><ForeName>Ruheng</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>College of Resources and Environment, South China Agricultural University, Guangzhou, 510642, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fan</LastName><ForeName>Jihong</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>College of Resources and Environment, South China Agricultural University, Guangzhou, 510642, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ye</LastName><ForeName>Hanming</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>College of Resources and Environment, South China Agricultural University, Guangzhou, 510642, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Shuwen</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. Electronic address: liusw@smu.edu.cn.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>02</Month><Day>20</Day></ArticleDate></Article><MedlineJournalInfo><Country>France</Country><MedlineTA>Eur J Med Chem</MedlineTA><NlmUniqueID>0420510</NlmUniqueID><ISSNLinking>0223-5234</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014315">Triterpenes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014326">Tropanes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C433845">chacotriose</NameOfSubstance></Chemical><Chemical><RegistryNumber>P3M2575F3F</RegistryNumber><NameOfSubstance UI="C005466">ursolic acid</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004285" MajorTopicYN="N">Dogs</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D057809" MajorTopicYN="N">HEK293 Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D053124" MajorTopicYN="N">Influenza A Virus, H5N1 Subtype</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D061985" MajorTopicYN="N">Madin Darby Canine Kidney Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013329" MajorTopicYN="N">Structure-Activity Relationship</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014315" MajorTopicYN="N">Triterpenes</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014326" MajorTopicYN="N">Tropanes</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D053586" MajorTopicYN="N">Virus Internalization</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">3-O-β-chacotriosyl saponins</Keyword><Keyword MajorTopicYN="N">H5N1 entry inhibitors</Keyword><Keyword MajorTopicYN="N">Structure–activity relationships</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2014</Year><Month>10</Month><Day>05</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2015</Year><Month>01</Month><Day>22</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2015</Year><Month>02</Month><Day>07</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2015</Year><Month>3</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2015</Year><Month>3</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2015</Year><Month>12</Month><Day>22</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">25728024</ArticleId><ArticleId IdType="pii">S0223-5234(15)00125-7</ArticleId><ArticleId IdType="doi">10.1016/j.ejmech.2015.02.029</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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