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Current drug treatments for these diseases have notable drawbacks and side effects, underscoring the pressing need for new medications with improved selectivity and reduced toxicity. Through structural modifications of both natural and synthetic compounds using click chemistry, researchers have been able to produce derivatives showing promising activity against these parasites. In this study, 21 novel 1,2,3\u2010triazole analogues of totarol were synthesized using\n                    <jats:italic>O<\/jats:italic>\n                    \u2010propargylated totarol derivatives and substituted arylazide. These compounds were characterized through various analytical techniques, including\n                    <jats:sup>1<\/jats:sup>\n                    H NMR,\n                    <jats:sup>13<\/jats:sup>\n                    C NMR, and HRMS. An x\u2010ray crystallographic study of compounds\n                    <jats:bold>4<\/jats:bold>\n                    and\n                    <jats:bold>6<\/jats:bold>\n                    was carried out to fully establish the structure of the newly prepared totarol derivatives. All synthesized compounds were then screened in\u00a0vitro for their antileishmanial activities against\n                    <jats:italic>Leishmania major<\/jats:italic>\n                    promastigotes, amastigotes, and\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    tachyzoites Out of the tested analogues, six compounds (\n                    <jats:bold>7c, 8b\u2013e<\/jats:bold>\n                    , and\n                    <jats:bold>9\u2009g<\/jats:bold>\n                    ) displayed antileishmanial activity against\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>L. major<\/jats:italic>\n                    <\/jats:styled-content>\n                    amastigotes with IC\n                    <jats:sub>50<\/jats:sub>\n                    17.3, 14.2, 13.1 18.2 13.2 and 17.3\u2009\u03bcg\u2009mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    respectively, while only\n                    <jats:bold>8e<\/jats:bold>\n                    gave antileishmanial activity against both promastigotes and amastigotes with IC\n                    <jats:sub>50<\/jats:sub>\n                    11.7 and 13.2\u2009\u03bcg\u2009mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    respectively. Additionally, the presence of a nitro group was correlated with enhanced antileishmanial activity. Moreover, a molecular docking study was conducted, focusing on\n                    <jats:bold>8e<\/jats:bold>\n                    , the most active antileishmanial compound, to elucidate its putative binding pattern at the active site of the selected leishmanial trypanothione reductase target.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70042","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T11:01:42Z","timestamp":1739444502000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Design, Hemisynthesis, Characterization, Molecular Docking, and Dynamics Evaluation of Novel Totarol\u20101,2,3\u2010Triazole Derivatives as Leishmaniasis and Toxoplasmosis Agents"],"prefix":"10.1111","volume":"105","author":[{"given":"Ayoub","family":"Boualli","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Chemistry, unit of Organic Synthesis and Molecular Physico\u2010Chemistry, Department of Chemistry, Faculty of Sciences Semlalia Universit\u00e9 Cadi Ayyad  Marrakech Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yassine","family":"Laamari","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Chemistry, unit of Organic Synthesis and Molecular Physico\u2010Chemistry, Department of Chemistry, Faculty of Sciences Semlalia Universit\u00e9 Cadi Ayyad  Marrakech Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1853-5372","authenticated-orcid":false,"given":"Abdoullah","family":"Bimoussa","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Chemistry, unit of Organic Synthesis and Molecular Physico\u2010Chemistry, Department of Chemistry, Faculty of Sciences Semlalia Universit\u00e9 Cadi Ayyad  Marrakech Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syeda Abida","family":"Ejaz","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry The Islamia University of Bahawalpur  Bahawalpur Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hafiz Muhammad","family":"Attaullah","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry The Islamia University of Bahawalpur  Bahawalpur Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelkhalek","family":"Riahi","sequence":"additional","affiliation":[{"name":"Institut de Chimie Mol\u00e9culaire de Reims CNRS UMR 7312 B\u00e2t. Euro\u2010 pol'Agro \u2010 Moulin de la Housse UFR Sciences  Reims France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Robert","sequence":"additional","affiliation":[{"name":"Institut de Chimie Mol\u00e9culaire de Reims CNRS UMR 7312 B\u00e2t. 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