{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T09:06:06Z","timestamp":1784106366122,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["Be2253\/8"],"award-info":[{"award-number":["Be2253\/8"]}],"id":[{"id":"10.13039\/501100001659","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":[[2026,7,14]]},"abstract":"<jats:p>\n                    Inhibition of the\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    formate\u2010nitrite transporter (PfFNT) has emerged as a promising strategy for antimalarial drug development. PfFNT inhibitors display high potency against blood\u2010stage parasites and have shown efficacy in vivo. Here, we demonstrate activity against liver\u2010stage parasites of the front\u2010running compound, (Z)\u20104,4,5,5,5\u2010pentafluoro\u20103\u2010hydroxy\u20101\u2010(pyridin\u20103\u2010yl)pent\u20102\u2010en\u20101\u2010one (BH267m), highlighting the potential for chemopreventive applications. Consequently, we investigated the formation of metal complexes of PfFNT inhibitors as a strategy to generate long\u2010acting depot formulations enabling sustained drug release. Complexes with Mg\n                    <jats:sup>2+<\/jats:sup>\n                    , Ca\n                    <jats:sup>2+<\/jats:sup>\n                    , and Zn\n                    <jats:sup>2+<\/jats:sup>\n                    were prepared via chelation through the pharmacophoric vinylogous acid moiety and characterized by spectroscopic methods. The resulting solids formed amorphous particles in the low micrometer range with metal\u2010dependent aqueous solubilities. In vitro release studies using a dialysis assay revealed sustained, near zero\u2010order ligand release, with zinc\u2010based complexes displaying particularly low solubility and slow release kinetics. Release rates varied by approximately one order of magnitude depending on metal ion and ligand structure. Simulated plasma concentrations suggested sustained exposure of one\u2010 to tenfold of the respective in vitro EC\n                    <jats:sub>50<\/jats:sub>\n                    values within the current ligand portfolio. These findings indicate that coordination of vinylogous acid motifs with metal ions may provide a basis for developing long\u2010acting depot formulations of chelating anti\u2010infective agents.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70356","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T16:28:24Z","timestamp":1782923304000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metal\u2013Drug Complexes as Long\u2010Release Application for Antimalarial PfFNT\u2010Inhibitors"],"prefix":"10.1002","volume":"21","author":[{"given":"Finn","family":"Tiedjens","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical and Medicinal Chemistry Kiel University  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Henke","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Medicinal Chemistry 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