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<ArticleSet>
  <Article>
    <Journal>
      <PublisherName>aaspjournal</PublisherName>
      <JournalTitle>Journal of Asian Association of Schools of Pharmacy</JournalTitle>
      <PISSN>I</PISSN>
      <EISSN>S</EISSN>
      <Volume-Issue>Volume 1 No.4</Volume-Issue>
      <PartNumber/>
      <IssueTopic>Multidisciplinary</IssueTopic>
      <IssueLanguage>English</IssueLanguage>
      <Season>October - December, 2012</Season>
      <SpecialIssue>N</SpecialIssue>
      <SupplementaryIssue>N</SupplementaryIssue>
      <IssueOA>Y</IssueOA>
      <PubDate>
        <Year>-0001</Year>
        <Month>11</Month>
        <Day>30</Day>
      </PubDate>
      <ArticleType>Pharmacy</ArticleType>
      <ArticleTitle>Isoindole-1,3-dione-based __ampersandsignalpha;,__ampersandsigngamma;-diketo acid bioisosteres as hepatitis C virus NS5B polymerase inhibitors</ArticleTitle>
      <SubTitle/>
      <ArticleLanguage>English</ArticleLanguage>
      <ArticleOA>Y</ArticleOA>
      <FirstPage>210</FirstPage>
      <LastPage>225</LastPage>
      <AuthorList>
        <Author>
          <FirstName>Ravindra Ramesh</FirstName>
          <LastName>Deore</LastName>
          <AuthorLanguage>English</AuthorLanguage>
          <Affiliation/>
          <CorrespondingAuthor>N</CorrespondingAuthor>
          <ORCID/>
          <FirstName>Ajit Dhananjay</FirstName>
          <LastName>Jagtap</LastName>
          <AuthorLanguage>English</AuthorLanguage>
          <Affiliation/>
          <CorrespondingAuthor>Y</CorrespondingAuthor>
          <ORCID/>
          <FirstName>Pei-Teh</FirstName>
          <LastName>Chang</LastName>
          <AuthorLanguage>English</AuthorLanguage>
          <Affiliation/>
          <CorrespondingAuthor>Y</CorrespondingAuthor>
          <ORCID/>
          <FirstName>WirunyaTrimethasil</FirstName>
          <AuthorLanguage>English</AuthorLanguage>
          <Affiliation/>
          <CorrespondingAuthor>Y</CorrespondingAuthor>
          <ORCID/>
          <FirstName>Ji-Wang</FirstName>
          <LastName>Chern</LastName>
          <AuthorLanguage>English</AuthorLanguage>
          <Affiliation/>
          <CorrespondingAuthor>Y</CorrespondingAuthor>
          <ORCID/>
        </Author>
      </AuthorList>
      <DOI/>
      <Abstract>Integration of 2-N-hydroxyl- and 2-N-benzoyl-1,3- diketo acid moieties into isoindole-1,3-dione led to the development of two series of hepatitis C virus NS5B polymerase inhibitors. Structural optimization to translate enzyme inhibitory activity to cellular cytotoxicity yielded compound 16c, a moderate enzyme inhibitor (IC50 = 27.3 µM) with selective toxicity to hepatitis C virus 1b replicon-containing Ava5 cells (EC50 = 18.0 µM). Binding experiments indicated that 16c (Kd = 1.25 µM) not only competed with fluorescein-labeled GTP for NS5B binding, but also displaced bound GTP from the polymerase active site.</Abstract>
      <AbstractLanguage>English</AbstractLanguage>
      <Keywords>Hepatitis C virus NS5B polymerase ?,?-diketo acid bioisostere isoindole-1,3-dione</Keywords>
      <URLs>
        <Abstract>https://aaspjournal.org/ubijournal-v1copy/journals/abstract.php?article_id=5945&amp;title=Isoindole-1,3-dione-based __ampersandsignalpha;,__ampersandsigngamma;-diketo acid bioisosteres as hepatitis C virus NS5B polymerase inhibitors</Abstract>
      </URLs>
      <References>
        <ReferencesarticleTitle>References</ReferencesarticleTitle>
        <ReferencesfirstPage>16</ReferencesfirstPage>
        <ReferenceslastPage>19</ReferenceslastPage>
        <References/>
      </References>
    </Journal>
  </Article>
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