{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T21:42:45Z","timestamp":1781300565146,"version":"3.54.1"},"reference-count":40,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,30]],"date-time":"2022-05-30T00:00:00Z","timestamp":1653868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004192","name":"NSTDA Researcher Chair","doi-asserted-by":"publisher","award":["P1850116"],"award-info":[{"award-number":["P1850116"]}],"id":[{"id":"10.13039\/501100004192","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004192","name":"NSTDA Researcher Chair","doi-asserted-by":"publisher","award":["P1951535"],"award-info":[{"award-number":["P1951535"]}],"id":[{"id":"10.13039\/501100004192","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004192","name":"NSTDA Researcher Chair","doi-asserted-by":"publisher","award":["NSF CHE-0850693"],"award-info":[{"award-number":["NSF CHE-0850693"]}],"id":[{"id":"10.13039\/501100004192","id-type":"DOI","asserted-by":"publisher"}]},{"name":"BIOTEC Platform","award":["P1850116"],"award-info":[{"award-number":["P1850116"]}]},{"name":"BIOTEC Platform","award":["P1951535"],"award-info":[{"award-number":["P1951535"]}]},{"name":"BIOTEC Platform","award":["NSF CHE-0850693"],"award-info":[{"award-number":["NSF CHE-0850693"]}]},{"name":"National Science Foundation","award":["P1850116"],"award-info":[{"award-number":["P1850116"]}]},{"name":"National Science Foundation","award":["P1951535"],"award-info":[{"award-number":["P1951535"]}]},{"name":"National Science Foundation","award":["NSF CHE-0850693"],"award-info":[{"award-number":["NSF CHE-0850693"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In the fight towards eradication of malaria, identifying compounds active against new drug targets constitutes a key approach. Plasmodium falciparum 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase (PfHPPK) has been advanced as a promising target, as being part of the parasite essential folate biosynthesis pathway while having no orthologue in the human genome. However, no drug discovery efforts have been reported on this enzyme. In this study, we conducted a three-step screening of our in-house antifolate library against PfHPPK using a newly designed PfHPPK-GFP protein construct. Combining virtual screening, differential scanning fluorimetry and enzymatic assay, we identified 14 compounds active against PfHPPK. Compounds\u2019 binding modes were investigated by molecular docking, suggesting competitive binding with the HMDP substrate. Cytotoxicity and in vitro ADME properties of hit compounds were also assessed, showing good metabolic stability and low toxicity. The most active compounds displayed low micromolar IC50 against drug-resistant parasites. The reported hit compounds constitute a good starting point for inhibitor development against PfHPPK, as an alternative approach to tackle the malaria parasite.<\/jats:p>","DOI":"10.3390\/molecules27113515","type":"journal-article","created":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T00:25:12Z","timestamp":1653956712000},"page":"3515","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Assay Development and Identification of the First Plasmodium falciparum 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase Inhibitors"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5758-3556","authenticated-orcid":false,"given":"Marie","family":"Hoarau","sequence":"first","affiliation":[{"name":"National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nattida","family":"Suwanakitti","sequence":"additional","affiliation":[{"name":"National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thaveechai","family":"Varatthan","sequence":"additional","affiliation":[{"name":"National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratthiya","family":"Thiabma","sequence":"additional","affiliation":[{"name":"National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roonglawan","family":"Rattanajak","sequence":"additional","affiliation":[{"name":"National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Netnapa","family":"Charoensetakul","sequence":"additional","affiliation":[{"name":"National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily K.","family":"Redman","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7236-0625","authenticated-orcid":false,"given":"Tanatorn","family":"Khotavivattana","sequence":"additional","affiliation":[{"name":"Center of Excellence in Natural Products Chemistry, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tirayut","family":"Vilaivan","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongyuth","family":"Yuthavong","sequence":"additional","affiliation":[{"name":"National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumalee","family":"Kamchonwongpaisan","sequence":"additional","affiliation":[{"name":"National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/j.drudis.2006.08.003","article-title":"Inhibitors of de Novo Folate Enzymes in Plasmodium Falciparum","volume":"11","author":"Nzila","year":"2006","journal-title":"Drug Discov. 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