Ishmail, Fatima-ZahraCoertzen, DinaTshabalala, SizweLeshabane, Meta KgaogeloDa Rocha, ShantéNjoroge, MathewGibhard, LiezlBirkholtz, Lyn-MarieWoodland, John G.Egan, Timothy J.Wicht, Kathryn J.Chibale, Kelly2025-03-052025-03-052025-03Ishmail, F.Z., Coertzen, D., Tshabalala, S. et al. 2025, 'Synthesis and SAR studies of acyl-thiourea platinum(II) complexes yield analogs with dual-stage antiplasmodium activity', ACS Medicinal Chemistry Letters, vol. 16, no. 3, pp. 428-535, doi : 10.1021/acsmedchemlett.4c00545.http://hdl.handle.net/2263/101346Mixed-ligand platinum(II) complexes incorporating bipyridine and acyl-thiourea ligands were synthesized and evaluated for their in vitro growth inhibitory activity against the human malaria parasite Plasmodium falciparum (Pf). The substituents at four distinct sites were varied to identify structure–activity relationships for this series. Most complexes displayed potent PfNF54 activity with IC50 values in the nanomolar range and favorable cytotoxicity profiles. Five complexes (C1, C11, C12, C15, and C17) exhibited activity against both the asexual blood and sexual (gametocyte) stage parasites, with another complex (C8) exhibiting activity against late-stage gametocytes only. In addition, the complexes showed comparable ABS potency against the PfK1 multidrug-resistant strain. The pharmacokinetic parameters of one analog (C6), which displayed good solubility and mouse microsomal metabolic stability, were measured. This work demonstrates the potential of acyl-thiourea platinum(II) complexes as selective, multistage-active antiplasmodium compounds as part of the search for new antimalarial agents.en© 2025 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0 .Mixed-ligand platinum(II) complexesBipyridine ligandsAcyl-thiourea ligandsIn vitro growthInhibitory activityHuman malaria parasitePlasmodium falciparum (Pf)SDG-03: Good health and well-beingLetterArticle