Exploration of structural and physicochemical requirements and search of virtual hits for aminopeptidase N inhibitors
Identifieur interne : 000587 ( Istex/Corpus ); précédent : 000586; suivant : 000588Exploration of structural and physicochemical requirements and search of virtual hits for aminopeptidase N inhibitors
Auteurs : Amit K. Halder ; Achintya Saha ; Tarun JhaSource :
- Molecular Diversity [ 1381-1991 ] ; 2013-02-01.
English descriptors
- KwdEn :
Abstract
Abstract: Aminopeptidase N (APN) inhibitors have been reported to be effective in treating of life threatening diseases including cancer. Validated ligand- and structure-based pharmacophore mapping approaches were combined with Bayesian modeling and recursive partitioning to identify structural and physicochemical requirements for highly active APN inhibitors. Based on the assumption that ligand- and structure-based pharmacophore models are complementary, the efficacy of ‘multiple pharmacophore screening’ for filtering true positive virtual hits was investigated. These multiple pharmacophore screening methods were utilized to search novel virtual hits for APN inhibition. The number of hits was refined and reduced by recursive partitioning, drug-likeliness, pharmacokinetic property prediction, and comparative molecular-docking studies. Four compounds were proposed as the potential virtual hits for APN enzyme inhibition.
Url:
DOI: 10.1007/s11030-013-9422-5
Links to Exploration step
ISTEX:C1CE20E6432CC47C5327756143AAF60466E1E3EALe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Exploration of structural and physicochemical requirements and search of virtual hits for aminopeptidase N inhibitors</title><author><name sortKey="Halder, Amit K" sort="Halder, Amit K" uniqKey="Halder A" first="Amit K." last="Halder">Amit K. Halder</name><affiliation><mods:affiliation>Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, P.O. Box 17020, 700032, Kolkata, India</mods:affiliation></affiliation></author><author><name sortKey="Saha, Achintya" sort="Saha, Achintya" uniqKey="Saha A" first="Achintya" last="Saha">Achintya Saha</name><affiliation><mods:affiliation>Department of Chemical Technology, University of Calcutta, 92, APC Ray Road, 700009, Kolkata, India</mods:affiliation></affiliation></author><author><name sortKey="Jha, Tarun" sort="Jha, Tarun" uniqKey="Jha T" first="Tarun" last="Jha">Tarun Jha</name><affiliation><mods:affiliation>Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, P.O. Box 17020, 700032, Kolkata, India</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: tjupharm@yahoo.com</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:C1CE20E6432CC47C5327756143AAF60466E1E3EA</idno><date when="2013" year="2013">2013</date><idno type="doi">10.1007/s11030-013-9422-5</idno><idno type="url">https://api.istex.fr/ark:/67375/VQC-5BTMRSJH-R/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">000587</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000587</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Exploration of structural and physicochemical requirements and search of virtual hits for aminopeptidase N inhibitors</title><author><name sortKey="Halder, Amit K" sort="Halder, Amit K" uniqKey="Halder A" first="Amit K." last="Halder">Amit K. Halder</name><affiliation><mods:affiliation>Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, P.O. Box 17020, 700032, Kolkata, India</mods:affiliation></affiliation></author><author><name sortKey="Saha, Achintya" sort="Saha, Achintya" uniqKey="Saha A" first="Achintya" last="Saha">Achintya Saha</name><affiliation><mods:affiliation>Department of Chemical Technology, University of Calcutta, 92, APC Ray Road, 700009, Kolkata, India</mods:affiliation></affiliation></author><author><name sortKey="Jha, Tarun" sort="Jha, Tarun" uniqKey="Jha T" first="Tarun" last="Jha">Tarun Jha</name><affiliation><mods:affiliation>Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, P.O. Box 17020, 700032, Kolkata, India</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: tjupharm@yahoo.com</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Molecular Diversity</title><title level="j" type="abbrev">Mol Divers</title><idno type="ISSN">1381-1991</idno><idno type="eISSN">1573-501X</idno><imprint><publisher>Springer Netherlands</publisher><pubPlace>Dordrecht</pubPlace><date type="published" when="2013-02-01">2013-02-01</date><biblScope unit="volume">17</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="123">123</biblScope><biblScope unit="page" to="137">137</biblScope></imprint><idno type="ISSN">1381-1991</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1381-1991</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aminopeptidase N</term><term>Bayesian modeling</term><term>Molecular docking</term><term>Pharmacophore mapping</term><term>Recursive partitioning</term><term>Virtual hits</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Aminopeptidase N (APN) inhibitors have been reported to be effective in treating of life threatening diseases including cancer. Validated ligand- and structure-based pharmacophore mapping approaches were combined with Bayesian modeling and recursive partitioning to identify structural and physicochemical requirements for highly active APN inhibitors. Based on the assumption that ligand- and structure-based pharmacophore models are complementary, the efficacy of ‘multiple pharmacophore screening’ for filtering true positive virtual hits was investigated. These multiple pharmacophore screening methods were utilized to search novel virtual hits for APN inhibition. The number of hits was refined and reduced by recursive partitioning, drug-likeliness, pharmacokinetic property prediction, and comparative molecular-docking studies. Four compounds were proposed as the potential virtual hits for APN enzyme inhibition.</div></front></TEI><istex><corpusName>springer-journals</corpusName><author><json:item><name>Amit K. Halder</name><affiliations><json:string>Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, P.O. Box 17020, 700032, Kolkata, India</json:string></affiliations></json:item><json:item><name>Achintya Saha</name><affiliations><json:string>Department of Chemical Technology, University of Calcutta, 92, APC Ray Road, 700009, Kolkata, India</json:string></affiliations></json:item><json:item><name>Tarun Jha</name><affiliations><json:string>Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, P.O. Box 17020, 700032, Kolkata, India</json:string><json:string>E-mail: tjupharm@yahoo.com</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Aminopeptidase N</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Pharmacophore mapping</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Bayesian modeling</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Recursive partitioning</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Molecular docking</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Virtual hits</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>APN : Aminopeptidase N</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>A : Hydrogen-bond acceptor</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>BD : Binding database</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>D : Hydrogen-bond donor</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MFASA : Molecular fractional polar surface area</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MPSA : Molecular polar surface area</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MW : Molecular weight</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>$$n$$ HBA : Number of hydrogen-bond acceptor</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>$$n$$ HBD : Number of hydrogen-bond donor</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>$$n$$ Fr : Number of fragments</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>$$n$$ RB : Number of rotatable bonds</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>$$n$$ PA : Number of positive atoms</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>$$n$$ R : Number of rings</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>$$n$$ ArR : Number of aromatic rings</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>P : Positive ionisable</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>R : Ring aromatic</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>RP : Recursive partition</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Y : Hydrophobic</value></json:item></subject><articleId><json:string>9422</json:string><json:string>s11030-013-9422-5</json:string></articleId><arkIstex>ark:/67375/VQC-5BTMRSJH-R</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>OriginalPaper</json:string></originalGenre><abstract>Abstract: Aminopeptidase N (APN) inhibitors have been reported to be effective in treating of life threatening diseases including cancer. Validated ligand- and structure-based pharmacophore mapping approaches were combined with Bayesian modeling and recursive partitioning to identify structural and physicochemical requirements for highly active APN inhibitors. Based on the assumption that ligand- and structure-based pharmacophore models are complementary, the efficacy of ‘multiple pharmacophore screening’ for filtering true positive virtual hits was investigated. These multiple pharmacophore screening methods were utilized to search novel virtual hits for APN inhibition. The number of hits was refined and reduced by recursive partitioning, drug-likeliness, pharmacokinetic property prediction, and comparative molecular-docking studies. Four compounds were proposed as the potential virtual hits for APN enzyme inhibition.</abstract><qualityIndicators><score>8.416</score><pdfWordCount>8286</pdfWordCount><pdfCharCount>54472</pdfCharCount><pdfVersion>1.4</pdfVersion><pdfPageCount>15</pdfPageCount><pdfPageSize>595.276 x 790.866 pts</pdfPageSize><refBibsNative>false</refBibsNative><abstractWordCount>118</abstractWordCount><abstractCharCount>932</abstractCharCount><keywordCount>24</keywordCount></qualityIndicators><title>Exploration of structural and physicochemical requirements and search of virtual hits for aminopeptidase N inhibitors</title><genre><json:string>research-article</json:string></genre><host><title>Molecular Diversity</title><language><json:string>unknown</json:string></language><publicationDate>2013</publicationDate><copyrightDate>2013</copyrightDate><issn><json:string>1381-1991</json:string></issn><eissn><json:string>1573-501X</json:string></eissn><journalId><json:string>11030</json:string></journalId><volume>17</volume><issue>1</issue><pages><first>123</first><last>137</last></pages><genre><json:string>journal</json:string></genre><subject><json:item><value>Biomedical and Life Sciences</value></json:item><json:item><value>Life Sciences</value></json:item><json:item><value>Biochemistry, general</value></json:item><json:item><value>Organic Chemistry</value></json:item><json:item><value>Polymer Sciences</value></json:item><json:item><value>Pharmacy</value></json:item></subject></host><ark><json:string>ark:/67375/VQC-5BTMRSJH-R</json:string></ark><publicationDate>2013</publicationDate><copyrightDate>2013</copyrightDate><doi><json:string>10.1007/s11030-013-9422-5</json:string></doi><id>C1CE20E6432CC47C5327756143AAF60466E1E3EA</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/ark:/67375/VQC-5BTMRSJH-R/fulltext.pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/ark:/67375/VQC-5BTMRSJH-R/bundle.zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/ark:/67375/VQC-5BTMRSJH-R/fulltext.tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Exploration of structural and physicochemical requirements and search of virtual hits for aminopeptidase N inhibitors</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher scheme="https://scientific-publisher.data.istex.fr">Springer Netherlands</publisher><pubPlace>Dordrecht</pubPlace><availability><licence><p>Springer Science+Business Media Dordrecht, 2013</p></licence><p scheme="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-3XSW68JL-F">springer</p></availability><date>2012-08-10</date></publicationStmt><notesStmt><note type="research-article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</note><note type="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note><note>Full-Length Paper</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Exploration of structural and physicochemical requirements and search of virtual hits for aminopeptidase N inhibitors</title><author xml:id="author-0000"><persName><forename type="first">Amit</forename><surname>Halder</surname></persName><affiliation>Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, P.O. Box 17020, 700032, Kolkata, India</affiliation></author><author xml:id="author-0001"><persName><forename type="first">Achintya</forename><surname>Saha</surname></persName><affiliation>Department of Chemical Technology, University of Calcutta, 92, APC Ray Road, 700009, Kolkata, India</affiliation></author><author xml:id="author-0002" corresp="yes"><persName><forename type="first">Tarun</forename><surname>Jha</surname></persName><email>tjupharm@yahoo.com</email><affiliation>Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, P.O. Box 17020, 700032, Kolkata, India</affiliation></author><idno type="istex">C1CE20E6432CC47C5327756143AAF60466E1E3EA</idno><idno type="ark">ark:/67375/VQC-5BTMRSJH-R</idno><idno type="DOI">10.1007/s11030-013-9422-5</idno><idno type="article-id">9422</idno><idno type="article-id">s11030-013-9422-5</idno></analytic><monogr><title level="j">Molecular Diversity</title><title level="j" type="abbrev">Mol Divers</title><idno type="pISSN">1381-1991</idno><idno type="eISSN">1573-501X</idno><idno type="journal-ID">true</idno><idno type="issue-article-count">15</idno><idno type="volume-issue-count">4</idno><imprint><publisher>Springer Netherlands</publisher><pubPlace>Dordrecht</pubPlace><date type="published" when="2013-02-01"></date><biblScope unit="volume">17</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="123">123</biblScope><biblScope unit="page" to="137">137</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2012-08-10</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Abstract: Aminopeptidase N (APN) inhibitors have been reported to be effective in treating of life threatening diseases including cancer. Validated ligand- and structure-based pharmacophore mapping approaches were combined with Bayesian modeling and recursive partitioning to identify structural and physicochemical requirements for highly active APN inhibitors. Based on the assumption that ligand- and structure-based pharmacophore models are complementary, the efficacy of ‘multiple pharmacophore screening’ for filtering true positive virtual hits was investigated. These multiple pharmacophore screening methods were utilized to search novel virtual hits for APN inhibition. The number of hits was refined and reduced by recursive partitioning, drug-likeliness, pharmacokinetic property prediction, and comparative molecular-docking studies. Four compounds were proposed as the potential virtual hits for APN enzyme inhibition.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Aminopeptidase N</term></item><item><term>Pharmacophore mapping</term></item><item><term>Bayesian modeling</term></item><item><term>Recursive partitioning</term></item><item><term>Molecular docking</term></item><item><term>Virtual hits</term></item></list></keywords></textClass><textClass><keywords scheme="keyword"><list><head>Abbreviations</head><item><term>APN</term><term>Aminopeptidase N</term></item><item><term>A</term><term>Hydrogen-bond acceptor</term></item><item><term>BD</term><term>Binding database</term></item><item><term>D</term><term>Hydrogen-bond donor</term></item><item><term>MFASA</term><term>Molecular fractional polar surface area</term></item><item><term>MPSA</term><term>Molecular polar surface area</term></item><item><term>MW</term><term>Molecular weight</term></item><item><term>$$n$$ HBA</term><term>Number of hydrogen-bond acceptor</term></item><item><term>$$n$$ HBD</term><term>Number of hydrogen-bond donor</term></item><item><term>$$n$$ Fr</term><term>Number of fragments</term></item><item><term>$$n$$ RB</term><term>Number of rotatable bonds</term></item><item><term>$$n$$ PA</term><term>Number of positive atoms</term></item><item><term>$$n$$ R</term><term>Number of rings</term></item><item><term>$$n$$ ArR</term><term>Number of aromatic rings</term></item><item><term>P</term><term>Positive ionisable</term></item><item><term>R</term><term>Ring aromatic</term></item><item><term>RP</term><term>Recursive partition</term></item><item><term>Y</term><term>Hydrophobic</term></item></list></keywords></textClass><textClass><keywords scheme="Journal-Subject-Collection"><list><label>SC3</label><item><term>Biomedical and Life Sciences</term></item></list></keywords></textClass><textClass><keywords scheme="Journal-Subject-Group"><list><label>SCL</label><item><term>Life Sciences</term></item><label>SCL14005</label><item><term>Biochemistry, general</term></item><label>SCC19007</label><item><term>Organic Chemistry</term></item><label>SCC22008</label><item><term>Polymer Sciences</term></item><label>SCF00008</label><item><term>Pharmacy</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2012-08-10">Created</change><change when="2013-02-01">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/VQC-5BTMRSJH-R/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus springer-journals not found" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="UTF-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//Springer-Verlag//DTD A++ V2.4//EN" URI="http://devel.springer.de/A++/V2.4/DTD/A++V2.4.dtd" name="istex:docType"></istex:docType><istex:document><Publisher><PublisherInfo><PublisherName>Springer Netherlands</PublisherName><PublisherLocation>Dordrecht</PublisherLocation><PublisherImprintName>Springer</PublisherImprintName></PublisherInfo><Journal OutputMedium="All"><JournalInfo JournalProductType="ArchiveJournal" NumberingStyle="Unnumbered"><JournalID>11030</JournalID><JournalPrintISSN>1381-1991</JournalPrintISSN><JournalElectronicISSN>1573-501X</JournalElectronicISSN><JournalTitle>Molecular Diversity</JournalTitle><JournalAbbreviatedTitle>Mol Divers</JournalAbbreviatedTitle><JournalSubjectGroup><JournalSubject Code="SCL" Type="Primary">Life Sciences</JournalSubject><JournalSubject Code="SCL14005" Priority="1" Type="Secondary">Biochemistry, general</JournalSubject><JournalSubject Code="SCC19007" Priority="2" Type="Secondary">Organic Chemistry</JournalSubject><JournalSubject Code="SCC22008" Priority="3" Type="Secondary">Polymer Sciences</JournalSubject><JournalSubject Code="SCF00008" Priority="4" Type="Secondary">Pharmacy</JournalSubject><SubjectCollection Code="SC3">Biomedical and Life Sciences</SubjectCollection></JournalSubjectGroup></JournalInfo><Volume OutputMedium="All"><VolumeInfo TocLevels="0" VolumeType="Regular"><VolumeIDStart>17</VolumeIDStart><VolumeIDEnd>17</VolumeIDEnd><VolumeIssueCount>4</VolumeIssueCount></VolumeInfo><Issue IssueType="Regular" OutputMedium="All"><IssueInfo IssueType="Regular" TocLevels="0"><IssueIDStart>1</IssueIDStart><IssueIDEnd>1</IssueIDEnd><IssueArticleCount>15</IssueArticleCount><IssueHistory><OnlineDate><Year>2013</Year><Month>2</Month><Day>5</Day></OnlineDate><PrintDate><Year>2013</Year><Month>2</Month><Day>4</Day></PrintDate><CoverDate><Year>2013</Year><Month>2</Month></CoverDate><PricelistYear>2013</PricelistYear></IssueHistory><IssueCopyright><CopyrightHolderName>Springer Science+Business Media Dordrecht</CopyrightHolderName><CopyrightYear>2013</CopyrightYear></IssueCopyright></IssueInfo><Article ID="s11030-013-9422-5" OutputMedium="All"><ArticleInfo ArticleType="OriginalPaper" ContainsESM="Yes" Language="En" NumberingStyle="Unnumbered" TocLevels="0"><ArticleID>9422</ArticleID><ArticleDOI>10.1007/s11030-013-9422-5</ArticleDOI><ArticleSequenceNumber>13</ArticleSequenceNumber><ArticleTitle Language="En" OutputMedium="All">Exploration of structural and physicochemical requirements and search of virtual hits for aminopeptidase N inhibitors</ArticleTitle><ArticleCategory>Full-Length Paper</ArticleCategory><ArticleFirstPage>123</ArticleFirstPage><ArticleLastPage>137</ArticleLastPage><ArticleHistory><RegistrationDate><Year>2013</Year><Month>1</Month><Day>7</Day></RegistrationDate><Received><Year>2012</Year><Month>8</Month><Day>10</Day></Received><Accepted><Year>2013</Year><Month>1</Month><Day>7</Day></Accepted><OnlineDate><Year>2013</Year><Month>1</Month><Day>23</Day></OnlineDate></ArticleHistory><ArticleCopyright><CopyrightHolderName>Springer Science+Business Media Dordrecht</CopyrightHolderName><CopyrightYear>2013</CopyrightYear></ArticleCopyright><ArticleGrants Type="Regular"><MetadataGrant Grant="OpenAccess"></MetadataGrant><AbstractGrant Grant="OpenAccess"></AbstractGrant><BodyPDFGrant Grant="Restricted"></BodyPDFGrant><BodyHTMLGrant Grant="Restricted"></BodyHTMLGrant><BibliographyGrant Grant="Restricted"></BibliographyGrant><ESMGrant Grant="Restricted"></ESMGrant></ArticleGrants></ArticleInfo><ArticleHeader><AuthorGroup><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Amit</GivenName><GivenName>K.</GivenName><FamilyName>Halder</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff2"><AuthorName DisplayOrder="Western"><GivenName>Achintya</GivenName><FamilyName>Saha</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1" CorrespondingAffiliationID="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Tarun</GivenName><FamilyName>Jha</FamilyName></AuthorName><Contact><Phone>+919433187443</Phone><Fax>+913324146927</Fax><Email>tjupharm@yahoo.com</Email></Contact></Author><Affiliation ID="Aff1"><OrgDivision>Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology</OrgDivision><OrgName>Jadavpur University</OrgName><OrgAddress><Postbox>P.O. Box 17020</Postbox><City>Kolkata</City><Postcode>700032</Postcode><Country Code="IN">India</Country></OrgAddress></Affiliation><Affiliation ID="Aff2"><OrgDivision>Department of Chemical Technology</OrgDivision><OrgName>University of Calcutta</OrgName><OrgAddress><Street>92, APC Ray Road</Street><City>Kolkata</City><Postcode>700009</Postcode><Country Code="IN">India</Country></OrgAddress></Affiliation></AuthorGroup><Abstract ID="Abs1" Language="En" OutputMedium="All"><Heading>Abstract</Heading><Para>Aminopeptidase N (APN) inhibitors have been reported to be effective in treating of life threatening diseases including cancer. Validated ligand- and structure-based pharmacophore mapping approaches were combined with Bayesian modeling and recursive partitioning to identify structural and physicochemical requirements for highly active APN inhibitors. Based on the assumption that ligand- and structure-based pharmacophore models are complementary, the efficacy of ‘multiple pharmacophore screening’ for filtering true positive virtual hits was investigated. These multiple pharmacophore screening methods were utilized to search novel virtual hits for APN inhibition. The number of hits was refined and reduced by recursive partitioning, drug-likeliness, pharmacokinetic property prediction, and comparative molecular-docking studies. Four compounds were proposed as the potential virtual hits for APN enzyme inhibition.</Para></Abstract><KeywordGroup Language="En" OutputMedium="All"><Heading>Keywords</Heading><Keyword>Aminopeptidase N</Keyword><Keyword>Pharmacophore mapping</Keyword><Keyword>Bayesian modeling</Keyword><Keyword>Recursive partitioning</Keyword><Keyword>Molecular docking</Keyword><Keyword>Virtual hits</Keyword></KeywordGroup><AbbreviationGroup><Heading>Abbreviations</Heading><DefinitionList><DefinitionListEntry><Term>APN</Term><Description><Para>Aminopeptidase N</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>A</Term><Description><Para>Hydrogen-bond acceptor</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>BD</Term><Description><Para>Binding database</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>D</Term><Description><Para>Hydrogen-bond donor</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>MFASA</Term><Description><Para>Molecular fractional polar surface area</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>MPSA</Term><Description><Para>Molecular polar surface area</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>MW</Term><Description><Para>Molecular weight</Para></Description></DefinitionListEntry><DefinitionListEntry><Term><InlineEquation ID="IEq1"><InlineMediaObject><ImageObject Color="BlackWhite" FileRef="11030_2013_9422_Article_IEq1.gif" Format="GIF" Rendition="HTML" Type="Linedraw"></ImageObject></InlineMediaObject><EquationSource Format="TEX">$$n$$</EquationSource></InlineEquation>HBA</Term><Description><Para>Number of hydrogen-bond acceptor</Para></Description></DefinitionListEntry><DefinitionListEntry><Term><InlineEquation ID="IEq2"><InlineMediaObject><ImageObject Color="BlackWhite" FileRef="11030_2013_9422_Article_IEq2.gif" Format="GIF" Rendition="HTML" Type="Linedraw"></ImageObject></InlineMediaObject><EquationSource Format="TEX">$$n$$</EquationSource></InlineEquation>HBD</Term><Description><Para>Number of hydrogen-bond donor</Para></Description></DefinitionListEntry><DefinitionListEntry><Term><InlineEquation ID="IEq3"><InlineMediaObject><ImageObject Color="BlackWhite" FileRef="11030_2013_9422_Article_IEq3.gif" Format="GIF" Rendition="HTML" Type="Linedraw"></ImageObject></InlineMediaObject><EquationSource Format="TEX">$$n$$</EquationSource></InlineEquation>Fr</Term><Description><Para>Number of fragments</Para></Description></DefinitionListEntry><DefinitionListEntry><Term><InlineEquation ID="IEq4"><InlineMediaObject><ImageObject Color="BlackWhite" FileRef="11030_2013_9422_Article_IEq4.gif" Format="GIF" Rendition="HTML" Type="Linedraw"></ImageObject></InlineMediaObject><EquationSource Format="TEX">$$n$$</EquationSource></InlineEquation>RB</Term><Description><Para>Number of rotatable bonds</Para></Description></DefinitionListEntry><DefinitionListEntry><Term><InlineEquation ID="IEq5"><InlineMediaObject><ImageObject Color="BlackWhite" FileRef="11030_2013_9422_Article_IEq5.gif" Format="GIF" Rendition="HTML" Type="Linedraw"></ImageObject></InlineMediaObject><EquationSource Format="TEX">$$n$$</EquationSource></InlineEquation>PA</Term><Description><Para>Number of positive atoms</Para></Description></DefinitionListEntry><DefinitionListEntry><Term><InlineEquation ID="IEq6"><InlineMediaObject><ImageObject Color="BlackWhite" FileRef="11030_2013_9422_Article_IEq6.gif" Format="GIF" Rendition="HTML" Type="Linedraw"></ImageObject></InlineMediaObject><EquationSource Format="TEX">$$n$$</EquationSource></InlineEquation>R</Term><Description><Para>Number of rings</Para></Description></DefinitionListEntry><DefinitionListEntry><Term><InlineEquation ID="IEq7"><InlineMediaObject><ImageObject Color="BlackWhite" FileRef="11030_2013_9422_Article_IEq7.gif" Format="GIF" Rendition="HTML" Type="Linedraw"></ImageObject></InlineMediaObject><EquationSource Format="TEX">$$n$$</EquationSource></InlineEquation>ArR</Term><Description><Para>Number of aromatic rings</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>P</Term><Description><Para>Positive ionisable</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>R</Term><Description><Para>Ring aromatic</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>RP</Term><Description><Para>Recursive partition</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>Y</Term><Description><Para>Hydrophobic</Para></Description></DefinitionListEntry></DefinitionList></AbbreviationGroup><ArticleNote Type="ESMHint"><Heading>Electronic supplementary material</Heading><SimplePara>The online version of this article (doi:<ExternalRef><RefSource>10.1007/s11030-013-9422-5</RefSource><RefTarget Address="10.1007/s11030-013-9422-5" TargetType="DOI"></RefTarget></ExternalRef>) contains supplementary material, which is available to authorized users.</SimplePara></ArticleNote></ArticleHeader><NoBody></NoBody></Article></Issue></Volume></Journal></Publisher></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Exploration of structural and physicochemical requirements and search of virtual hits for aminopeptidase N inhibitors</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Exploration of structural and physicochemical requirements and search of virtual hits for aminopeptidase N inhibitors</title></titleInfo><name type="personal"><namePart type="given">Amit</namePart><namePart type="given">K.</namePart><namePart type="family">Halder</namePart><affiliation>Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, P.O. Box 17020, 700032, Kolkata, India</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Achintya</namePart><namePart type="family">Saha</namePart><affiliation>Department of Chemical Technology, University of Calcutta, 92, APC Ray Road, 700009, Kolkata, India</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal" displayLabel="corresp"><namePart type="given">Tarun</namePart><namePart type="family">Jha</namePart><affiliation>Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, P.O. Box 17020, 700032, Kolkata, India</affiliation><affiliation>E-mail: tjupharm@yahoo.com</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="OriginalPaper" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>Springer Netherlands</publisher><place><placeTerm type="text">Dordrecht</placeTerm></place><dateCreated encoding="w3cdtf">2012-08-10</dateCreated><dateIssued encoding="w3cdtf">2013-02-01</dateIssued><copyrightDate encoding="w3cdtf">2013</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><abstract lang="en">Abstract: Aminopeptidase N (APN) inhibitors have been reported to be effective in treating of life threatening diseases including cancer. Validated ligand- and structure-based pharmacophore mapping approaches were combined with Bayesian modeling and recursive partitioning to identify structural and physicochemical requirements for highly active APN inhibitors. Based on the assumption that ligand- and structure-based pharmacophore models are complementary, the efficacy of ‘multiple pharmacophore screening’ for filtering true positive virtual hits was investigated. These multiple pharmacophore screening methods were utilized to search novel virtual hits for APN inhibition. The number of hits was refined and reduced by recursive partitioning, drug-likeliness, pharmacokinetic property prediction, and comparative molecular-docking studies. Four compounds were proposed as the potential virtual hits for APN enzyme inhibition.</abstract><note>Full-Length Paper</note><subject lang="en"><genre>Keywords</genre><topic>Aminopeptidase N</topic><topic>Pharmacophore mapping</topic><topic>Bayesian modeling</topic><topic>Recursive partitioning</topic><topic>Molecular docking</topic><topic>Virtual hits</topic></subject><subject><genre>Abbreviations</genre><topic>APN : Aminopeptidase N</topic><topic>A : Hydrogen-bond acceptor</topic><topic>BD : Binding database</topic><topic>D : Hydrogen-bond donor</topic><topic>MFASA : Molecular fractional polar surface area</topic><topic>MPSA : Molecular polar surface area</topic><topic>MW : Molecular weight</topic><topic>$$n$$ HBA : Number of hydrogen-bond acceptor</topic><topic>$$n$$ HBD : Number of hydrogen-bond donor</topic><topic>$$n$$ Fr : Number of fragments</topic><topic>$$n$$ RB : Number of rotatable bonds</topic><topic>$$n$$ PA : Number of positive atoms</topic><topic>$$n$$ R : Number of rings</topic><topic>$$n$$ ArR : Number of aromatic rings</topic><topic>P : Positive ionisable</topic><topic>R : Ring aromatic</topic><topic>RP : Recursive partition</topic><topic>Y : Hydrophobic</topic></subject><relatedItem type="host"><titleInfo><title>Molecular Diversity</title></titleInfo><titleInfo type="abbreviated"><title>Mol Divers</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><originInfo><publisher>Springer</publisher><dateIssued encoding="w3cdtf">2013-02-05</dateIssued><copyrightDate encoding="w3cdtf">2013</copyrightDate></originInfo><subject><genre>Journal-Subject-Collection</genre><topic authority="SpringerSubjectCodes" authorityURI="SC3">Biomedical and Life Sciences</topic></subject><subject><genre>Journal-Subject-Group</genre><topic authority="SpringerSubjectCodes" authorityURI="SCL">Life Sciences</topic><topic authority="SpringerSubjectCodes" authorityURI="SCL14005">Biochemistry, general</topic><topic authority="SpringerSubjectCodes" authorityURI="SCC19007">Organic Chemistry</topic><topic authority="SpringerSubjectCodes" authorityURI="SCC22008">Polymer Sciences</topic><topic authority="SpringerSubjectCodes" authorityURI="SCF00008">Pharmacy</topic></subject><identifier type="ISSN">1381-1991</identifier><identifier type="eISSN">1573-501X</identifier><identifier type="JournalID">11030</identifier><identifier type="IssueArticleCount">15</identifier><identifier type="VolumeIssueCount">4</identifier><part><date>2013</date><detail type="volume"><number>17</number><caption>vol.</caption></detail><detail type="issue"><number>1</number><caption>no.</caption></detail><extent unit="pages"><start>123</start><end>137</end></extent></part><recordInfo><recordOrigin>Springer Science+Business Media Dordrecht, 2013</recordOrigin></recordInfo></relatedItem><identifier type="istex">C1CE20E6432CC47C5327756143AAF60466E1E3EA</identifier><identifier type="ark">ark:/67375/VQC-5BTMRSJH-R</identifier><identifier type="DOI">10.1007/s11030-013-9422-5</identifier><identifier type="ArticleID">9422</identifier><identifier type="ArticleID">s11030-013-9422-5</identifier><accessCondition type="use and reproduction" contentType="copyright">Springer Science+Business Media Dordrecht, 2013</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-3XSW68JL-F">springer</recordContentSource><recordOrigin>Springer Science+Business Media Dordrecht, 2013</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/VQC-5BTMRSJH-R/record.json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/CovidV1/Data/Istex/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000587 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Istex/Corpus/biblio.hfd -nk 000587 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= CovidV1
|flux= Istex
|étape= Corpus
|type= RBID
|clé= ISTEX:C1CE20E6432CC47C5327756143AAF60466E1E3EA
|texte= Exploration of structural and physicochemical requirements and search of virtual hits for aminopeptidase N inhibitors
}}
| This area was generated with Dilib version V0.6.33. |  |