<?xml version="1.0" encoding="utf-8"?>
<TEI xmlns="http://www.tei-c.org/ns/1.0" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:hal="http://hal.archives-ouvertes.fr/" xmlns:gml="http://www.opengis.net/gml/3.3/" xmlns:gmlce="http://www.opengis.net/gml/3.3/ce" version="1.1" xsi:schemaLocation="http://www.tei-c.org/ns/1.0 http://api.archives-ouvertes.fr/documents/aofr-sword.xsd">
  <teiHeader>
    <fileDesc>
      <titleStmt>
        <title>HAL TEI export of hal-05137600</title>
      </titleStmt>
      <publicationStmt>
        <distributor>CCSD</distributor>
        <availability status="restricted">
          <licence target="https://creativecommons.org/publicdomain/zero/1.0/">CC0 1.0 - Universal</licence>
        </availability>
        <date when="2026-05-15T19:32:16+02:00"/>
      </publicationStmt>
      <sourceDesc>
        <p part="N">HAL API Platform</p>
      </sourceDesc>
    </fileDesc>
  </teiHeader>
  <text>
    <body>
      <listBibl>
        <biblFull>
          <titleStmt>
            <title xml:lang="en">Design, Synthesis and Antiplasmodial Activities of a Library of Fluorine-Based 3-Benzylmenadiones</title>
            <author role="aut">
              <persName>
                <forename type="first">Matthieu</forename>
                <surname>Roignant</surname>
              </persName>
              <email type="md5">466e82b00ff21dc86562bc8a59081632</email>
              <email type="domain">unistra.fr</email>
              <idno type="idhal" notation="numeric">1557443</idno>
              <idno type="halauthorid" notation="string">1823659-1557443</idno>
              <affiliation ref="#struct-529618"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Jimmy</forename>
                <surname>Richard</surname>
              </persName>
              <email type="md5">9b9d7a6d9a834c1c4819af29a93a924e</email>
              <email type="domain">unistra.fr</email>
              <idno type="idhal" notation="numeric">1041722</idno>
              <idno type="halauthorid" notation="string">1501282-1041722</idno>
              <idno type="IDREF">https://www.idref.fr/249757052</idno>
              <affiliation ref="#struct-529618"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Maxime</forename>
                <surname>Donzel</surname>
              </persName>
              <email type="md5">d8f8c9c3d13cc68755d2d77e4bdd57fa</email>
              <email type="domain">unistra.fr</email>
              <idno type="idhal" notation="numeric">1100462</idno>
              <idno type="halauthorid" notation="string">1671649-1100462</idno>
              <idno type="IDREF">https://www.idref.fr/262292181</idno>
              <idno type="ORCID">https://orcid.org/0009-0006-6292-9749</idno>
              <affiliation ref="#struct-529618"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Matthias</forename>
                <surname>Rottmann</surname>
              </persName>
              <email type="md5">326c219f05dc4fcac783fb430a1e8531</email>
              <email type="domain">swisstph.ch</email>
              <idno type="idhal" notation="numeric">1515210</idno>
              <idno type="halauthorid" notation="string">2384312-1515210</idno>
              <idno type="ORCID">https://orcid.org/0000-0002-2207-7899</idno>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Pascal</forename>
                <surname>Mäser</surname>
              </persName>
              <email type="md5">099f2e4f88ead6d7c8f18a6f55e526e6</email>
              <email type="domain">swisstph.ch</email>
              <idno type="idhal" notation="numeric">1384564</idno>
              <idno type="halauthorid" notation="string">519080-1384564</idno>
              <idno type="ORCID">https://orcid.org/0000-0003-3122-1941</idno>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Elisabeth</forename>
                <surname>Davioud-Charvet</surname>
              </persName>
              <email type="md5">95517db76b25471ad1837d63c09c136e</email>
              <email type="domain">unistra.fr</email>
              <idno type="idhal" notation="string">e-davioud-charvet</idno>
              <idno type="idhal" notation="numeric">740975</idno>
              <idno type="halauthorid" notation="string">45271-740975</idno>
              <idno type="RESEARCHERID">http://www.researcherid.com/rid/I-3805-2013</idno>
              <idno type="ORCID">https://orcid.org/0000-0001-7026-4034</idno>
              <idno type="IDREF">https://www.idref.fr/100470602</idno>
              <idno type="RESEARCHERID">http://www.researcherid.com/rid/http://www.researcherid.com/rid/I-3805-2013</idno>
              <affiliation ref="#struct-529618"/>
            </author>
            <editor role="depositor">
              <persName>
                <forename>Elisabeth</forename>
                <surname>Davioud-Charvet</surname>
              </persName>
              <email type="md5">95517db76b25471ad1837d63c09c136e</email>
              <email type="domain">unistra.fr</email>
            </editor>
          </titleStmt>
          <editionStmt>
            <edition n="v1" type="current">
              <date type="whenSubmitted">2025-07-01 10:34:17</date>
              <date type="whenModified">2025-08-19 03:17:05</date>
              <date type="whenReleased">2025-07-09 10:07:06</date>
              <date type="whenProduced">2025-06-03</date>
              <date type="whenEndEmbargoed">2025-07-01</date>
              <ref type="file" target="https://hal.science/hal-05137600v1/document">
                <date notBefore="2025-07-01"/>
              </ref>
              <ref type="file" subtype="greenPublisher" n="1" target="https://hal.science/hal-05137600v1/file/molecules2025_6-F-bMDs.pdf" id="file-5137600-4438273">
                <date notBefore="2025-07-01"/>
              </ref>
              <ref type="annex" n="0" target="https://hal.science/hal-05137600v1/file/Molecules_ESI_V11_R2_CLEAN.pdf" id="file-5137600-4438274">
                <date notBefore="2025-07-01"/>
              </ref>
            </edition>
            <respStmt>
              <resp>contributor</resp>
              <name key="30533">
                <persName>
                  <forename>Elisabeth</forename>
                  <surname>Davioud-Charvet</surname>
                </persName>
                <email type="md5">95517db76b25471ad1837d63c09c136e</email>
                <email type="domain">unistra.fr</email>
              </name>
            </respStmt>
          </editionStmt>
          <publicationStmt>
            <distributor>CCSD</distributor>
            <idno type="halId">hal-05137600</idno>
            <idno type="halUri">https://hal.science/hal-05137600</idno>
            <idno type="halBibtex">roignant:hal-05137600</idno>
            <idno type="halRefHtml">&lt;i&gt;Molecules&lt;/i&gt;, 2025, 30 (11), pp.2446. &lt;a target="_blank" href="https://dx.doi.org/10.3390/molecules30112446"&gt;&amp;#x27E8;10.3390/molecules30112446&amp;#x27E9;&lt;/a&gt;</idno>
            <idno type="halRef">Molecules, 2025, 30 (11), pp.2446. &amp;#x27E8;10.3390/molecules30112446&amp;#x27E9;</idno>
            <availability status="restricted">
              <licence target="https://creativecommons.org/licenses/by/4.0/">CC BY 4.0 - Attribution<ref corresp="#file-5137600-4438273"/><ref corresp="#file-5137600-4438274"/></licence>
            </availability>
          </publicationStmt>
          <seriesStmt>
            <idno type="stamp" n="CNRS">CNRS - Centre national de la recherche scientifique</idno>
            <idno type="stamp" n="UNIV-STRASBG">Université de Strasbourg</idno>
            <idno type="stamp" n="INC-CNRS">Institut de Chimie du CNRS</idno>
            <idno type="stamp" n="SITE-ALSACE">Archive ouverte du site Alsace</idno>
            <idno type="stamp" n="UNIVOAK">UNIVOAK</idno>
            <idno type="stamp" n="UMR7042">Laboratoire d'innovation moléculaire et applications</idno>
          </seriesStmt>
          <notesStmt>
            <note type="audience" n="2">International</note>
            <note type="popular" n="0">No</note>
            <note type="peer" n="1">Yes</note>
          </notesStmt>
          <sourceDesc>
            <biblStruct>
              <analytic>
                <title xml:lang="en">Design, Synthesis and Antiplasmodial Activities of a Library of Fluorine-Based 3-Benzylmenadiones</title>
                <author role="aut">
                  <persName>
                    <forename type="first">Matthieu</forename>
                    <surname>Roignant</surname>
                  </persName>
                  <email type="md5">466e82b00ff21dc86562bc8a59081632</email>
                  <email type="domain">unistra.fr</email>
                  <idno type="idhal" notation="numeric">1557443</idno>
                  <idno type="halauthorid" notation="string">1823659-1557443</idno>
                  <affiliation ref="#struct-529618"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Jimmy</forename>
                    <surname>Richard</surname>
                  </persName>
                  <email type="md5">9b9d7a6d9a834c1c4819af29a93a924e</email>
                  <email type="domain">unistra.fr</email>
                  <idno type="idhal" notation="numeric">1041722</idno>
                  <idno type="halauthorid" notation="string">1501282-1041722</idno>
                  <idno type="IDREF">https://www.idref.fr/249757052</idno>
                  <affiliation ref="#struct-529618"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Maxime</forename>
                    <surname>Donzel</surname>
                  </persName>
                  <email type="md5">d8f8c9c3d13cc68755d2d77e4bdd57fa</email>
                  <email type="domain">unistra.fr</email>
                  <idno type="idhal" notation="numeric">1100462</idno>
                  <idno type="halauthorid" notation="string">1671649-1100462</idno>
                  <idno type="IDREF">https://www.idref.fr/262292181</idno>
                  <idno type="ORCID">https://orcid.org/0009-0006-6292-9749</idno>
                  <affiliation ref="#struct-529618"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Matthias</forename>
                    <surname>Rottmann</surname>
                  </persName>
                  <email type="md5">326c219f05dc4fcac783fb430a1e8531</email>
                  <email type="domain">swisstph.ch</email>
                  <idno type="idhal" notation="numeric">1515210</idno>
                  <idno type="halauthorid" notation="string">2384312-1515210</idno>
                  <idno type="ORCID">https://orcid.org/0000-0002-2207-7899</idno>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Pascal</forename>
                    <surname>Mäser</surname>
                  </persName>
                  <email type="md5">099f2e4f88ead6d7c8f18a6f55e526e6</email>
                  <email type="domain">swisstph.ch</email>
                  <idno type="idhal" notation="numeric">1384564</idno>
                  <idno type="halauthorid" notation="string">519080-1384564</idno>
                  <idno type="ORCID">https://orcid.org/0000-0003-3122-1941</idno>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Elisabeth</forename>
                    <surname>Davioud-Charvet</surname>
                  </persName>
                  <email type="md5">95517db76b25471ad1837d63c09c136e</email>
                  <email type="domain">unistra.fr</email>
                  <idno type="idhal" notation="string">e-davioud-charvet</idno>
                  <idno type="idhal" notation="numeric">740975</idno>
                  <idno type="halauthorid" notation="string">45271-740975</idno>
                  <idno type="RESEARCHERID">http://www.researcherid.com/rid/I-3805-2013</idno>
                  <idno type="ORCID">https://orcid.org/0000-0001-7026-4034</idno>
                  <idno type="IDREF">https://www.idref.fr/100470602</idno>
                  <idno type="RESEARCHERID">http://www.researcherid.com/rid/http://www.researcherid.com/rid/I-3805-2013</idno>
                  <affiliation ref="#struct-529618"/>
                </author>
              </analytic>
              <monogr>
                <idno type="halJournalId" status="VALID">17196</idno>
                <idno type="issn">1420-3049</idno>
                <title level="j">Molecules</title>
                <imprint>
                  <publisher>MDPI</publisher>
                  <biblScope unit="volume">30</biblScope>
                  <biblScope unit="issue">11</biblScope>
                  <biblScope unit="pp">2446</biblScope>
                  <date type="datePub">2025-06-03</date>
                </imprint>
              </monogr>
              <idno type="doi">10.3390/molecules30112446</idno>
            </biblStruct>
          </sourceDesc>
          <profileDesc>
            <langUsage>
              <language ident="en">English</language>
            </langUsage>
            <textClass>
              <keywords scheme="author">
                <term xml:lang="en">plasmodione</term>
                <term xml:lang="en">menadione</term>
                <term xml:lang="en">fluorine</term>
                <term xml:lang="en">benzylation</term>
                <term xml:lang="en">antiplasmodial</term>
              </keywords>
              <classCode scheme="halDomain" n="chim">Chemical Sciences</classCode>
              <classCode scheme="halDomain" n="sdv">Life Sciences [q-bio]</classCode>
              <classCode scheme="halTypology" n="ART">Journal articles</classCode>
              <classCode scheme="halOldTypology" n="ART">Journal articles</classCode>
              <classCode scheme="halTreeTypology" n="ART">Journal articles</classCode>
            </textClass>
            <abstract xml:lang="en">
              <p>Plasmodione is a potent early antiplasmodial compound. A metabolic study on mice treated with plasmodione revealed that 6-hydroxy–plasmodione was the main metabolite eliminated in the urine of treated mice. To block the metabolic pathway in the host, the introduction of fluorine at C-6 of the 3-benzylmenadione core was applied and showed potent antiplasmodial activity similar to that of the plasmodione analogue in vitro. In this work, a library of 38 6-fluoro-3-benzylmenadione analogues (a series) was constructed by incorporating structurally diverse groups in place of the 4-(trifluoromethyl) substituent present in the antiplasmodial plasmodione, via three synthetic routes. All new compounds were tested against the P. falciparum NF54 strain and for cytotoxicity with the rat L6 line. With a fluorine atom at C-6, A-a-21 was revealed to be the only compound from the a series, superior to the 6-H- analogue from the b series, with an IC50 value of 70 nM versus 200 nM. Then, five other fluorine-based 3-benzylmenadiones, in which the fluorine was introduced in various positions of the 3-benzylmenadione core, were synthetized to assist our understanding of the impact of fluorine on antiplasmodial potencies in vitro; in particular, the aim here was to compare the effects of human serum and P. berghei species in these drug screens. This was also conducted in vivo with the P. berghei-infected mouse model. In the P. berghei species assay, PD and the 4′-fluoro-3′-trifluoromethyl-benzylmenadione A-b-9 exhibited a similar antiplasmodial behavior toward P. falciparum versus P. berghei. In the human serum versus Albumax assays, only the 6-fluoro–plasmodione showed a lower shift factor between Albumax assays and human serum conditions, suggesting a lower protein binding for the 6-F-PD compared to plasmodione or A-b-9. In vivo, 6-fluoro–plasmodione proved to be the most potent 3-benzylmenadione, reducing parasitemia by 50% after oral administration at 50 mg/kg.</p>
            </abstract>
          </profileDesc>
        </biblFull>
      </listBibl>
    </body>
    <back>
      <listOrg type="structures">
        <org type="laboratory" xml:id="struct-529618" status="VALID">
          <idno type="IdRef">230285996</idno>
          <idno type="RNSR">201822682F</idno>
          <idno type="ROR">https://ror.org/030d6wr93</idno>
          <idno type="Wikidata">Q52607321</idno>
          <orgName>Laboratoire d'innovation moléculaire et applications</orgName>
          <orgName type="acronym">LIMA</orgName>
          <date type="start">2018-01-01</date>
          <desc>
            <address>
              <addrLine>25 Rue Becquerel 67087 Strasbourg Cedex 2</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://lima.unistra.fr/</ref>
          </desc>
          <listRelation>
            <relation active="#struct-199013" type="direct"/>
            <relation active="#struct-237692" type="direct"/>
            <relation active="#struct-341038" type="direct"/>
            <relation name="UMR7042" active="#struct-441569" type="direct"/>
          </listRelation>
        </org>
        <org type="institution" xml:id="struct-199013" status="VALID">
          <idno type="IdRef">131056549</idno>
          <idno type="ROR">https://ror.org/00pg6eq24</idno>
          <orgName>Université de Strasbourg</orgName>
          <orgName type="acronym">UNISTRA</orgName>
          <desc>
            <address>
              <addrLine>4 rue Blaise Pascal - CS 90032 - 67081 Strasbourg cedex</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">https://www.unistra.fr/</ref>
          </desc>
        </org>
        <org type="institution" xml:id="struct-237692" status="VALID">
          <idno type="IdRef">026403250</idno>
          <idno type="ISNI">0000000404735039</idno>
          <idno type="ROR">https://ror.org/04k8k6n84</idno>
          <orgName>Université de Haute-Alsace (UHA) Mulhouse - Colmar</orgName>
          <orgName type="acronym">Université de Haute-Alsace (UHA)</orgName>
          <desc>
            <address>
              <addrLine>2, rue des Frères Lumière F-68093 Mulhouse Cedex</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.uha.fr/</ref>
          </desc>
        </org>
        <org type="institution" xml:id="struct-341038" status="VALID">
          <idno type="IdRef">232435103</idno>
          <idno type="ISNI">000000010626358X</idno>
          <idno type="ROR">https://ror.org/02cte4b68</idno>
          <orgName>Institut de Chimie - CNRS Chimie</orgName>
          <orgName type="acronym">INC-CNRS</orgName>
          <date type="start">2009-10-01</date>
          <desc>
            <address>
              <addrLine>CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE3 rue Michel-Ange75794 PARIS CEDEX 16 - France</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.cnrs.fr/inc</ref>
          </desc>
        </org>
        <org type="regroupinstitution" xml:id="struct-441569" status="VALID">
          <idno type="IdRef">02636817X</idno>
          <idno type="ISNI">0000000122597504</idno>
          <idno type="ROR">https://ror.org/02feahw73</idno>
          <orgName>Centre National de la Recherche Scientifique</orgName>
          <orgName type="acronym">CNRS</orgName>
          <date type="start">1939-10-19</date>
          <desc>
            <address>
              <country key="FR"/>
            </address>
            <ref type="url">https://www.cnrs.fr/</ref>
          </desc>
        </org>
      </listOrg>
    </back>
  </text>
</TEI>