{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T02:37:46Z","timestamp":1783823866812,"version":"3.55.0"},"reference-count":22,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T00:00:00Z","timestamp":1667347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001336","name":"University of the Witwatersrand, Johannesburg","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001336","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2022,11,18]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A series of 5\u2010[(phenethylamino)methyl]pyrimidine\u20102,4\u2010diamines were assessed <jats:italic>in silico<\/jats:italic> as potential inhibitors of <jats:italic>Plasmodium falciparum<\/jats:italic> dihydrofolate reductase (<jats:italic>Pf<\/jats:italic>DHFR), synthesised and tested for inhibitory activity against <jats:italic>Pf<\/jats:italic>DHFR <jats:italic>in\u2005vitro<\/jats:italic>. The compounds displayed promising inhibitory activity against both wild\u2010type (<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub> 1.3\u2013243\u2005nM) and quadruple mutant (<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub> 13\u2013208\u2005nM) <jats:italic>Pf<\/jats:italic>DHFR in the biochemical enzyme assay, but were less potent in the whole\u2010cell <jats:italic>P. falciparum<\/jats:italic> assay (IC<jats:sub>50<\/jats:sub>(TM4\/8.2) 0.4\u201328\u2005\u03bcM; IC<jats:sub>50<\/jats:sub>(V1S) 3.7\u201354\u2005\u03bcM). Further investigation into the pharmacokinetic properties of these compounds may guide the development of more potent analogues.<\/jats:p>","DOI":"10.1002\/cmdc.202200418","type":"journal-article","created":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T07:04:01Z","timestamp":1664867041000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Molecular Docking Studies, Synthesis and Biological Evaluation of Substituted Pyrimidine\u20102,4\u2010diamines as Inhibitors of <i>Plasmodium falciparum<\/i> Dihydrofolate Reductase"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5652-5533","authenticated-orcid":false,"given":"Khonzisizwe","family":"Somandi","sequence":"first","affiliation":[{"name":"Molecular Sciences Institute School of Chemistry University of the Witwatersrand  Private Bag 3, PO WITS 2050 South Africa"},{"name":"WITS Research Institute for Malaria (WRIM) University of 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