Novel inhibitors of Plasmodium Phosphatidylinositol 4-kinase IIIβ with low propensity for resistance : life cycle stage activity and in vivo efficacy in a humanized mouse malaria infection model

dc.contributor.authorDziwornu, Godwin A.
dc.contributor.authorMmonwa, Mmakwena M.
dc.contributor.authorCoertzen, Dina
dc.contributor.authorKrugmann, Liezl
dc.contributor.authorSalomane, Nicolaas
dc.contributor.authorLeshabane, Meta
dc.contributor.authorThomas, Jean Argyle
dc.contributor.authorDa Rocha, Shanté
dc.contributor.authorReader, Janette
dc.contributor.authorMasike, Keabetswe
dc.contributor.authorNjoroge, Mathew
dc.contributor.authorSevilleno, Nicole
dc.contributor.authorCoyle, Rachael
dc.contributor.authorBoonyalai, Nonlawat
dc.contributor.authorMayville, Emily
dc.contributor.authorLee, Marcus C.S.
dc.contributor.authorFidock, David A.
dc.contributor.authorCoulson, Lauren B.
dc.contributor.authorWoodland, John G.
dc.contributor.authorWicht, Kathryn J.
dc.contributor.authorGhorpade, Sandeep R.
dc.contributor.authorBirkholtz, Lyn-Marie
dc.contributor.authorChibale, Kelly
dc.date.accessioned2025-11-18T07:41:09Z
dc.date.available2025-11-18T07:41:09Z
dc.date.issued2025-08
dc.descriptionSUPPORTING INFORMATION 1. Synthesis of intermediates; analytical spectra of compounds profiled in vivo; parasitology methods; PvPI4K and human kinase assays; in vitro ADME assays, and mouse pharmacokinetic and in vivo efficacy studies (PDF). SUPPORTING INFORMATION 2. In vitro data of all final compounds (mean IC50 values ± standard deviation (SD) or standard error (SE)) (CSV). SUPPORTING INFORMATION 3. Molecular formula strings (CSV).
dc.description.abstractPlease read abstract in the article.
dc.description.departmentBiochemistry, Genetics and Microbiology (BGM)
dc.description.departmentUP Centre for Sustainable Malaria Control (UP CSMC)
dc.description.librarianhj2025
dc.description.sdgSDG-03: Good health and well-being
dc.description.sponsorshipThe University of Cape Town, South African Medical Research Council (SAMRC), and South African Research Chairs Initiative (SARChI) of the Department of Science and Innovation (DSI), administered through the South African National Research Foundation (NRF), are gratefully acknowledged for support. The Neville Isdell Chair in African-centric Drug Discovery and Development funded by Neville Isdell; the transmission-blocking assay platform was supported by grants from the Medicines for Malaria Venture, the SAMRC, and the DSI SARChI Grants managed by the NRF; the Plasmodium AReBar assay platform was supported by Medicines for Malaria Venture; the Plasmodium kinase platform was supported by the Future Leaders−African Independent Research (FLAIR) Fellowship Programme, a partnership between the African Academy of Sciences and the Royal Society funded by the UK Government’s Global Challenges Research; the in vivo studies were supported by the Global Health Grants received from the Bill and Melinda Gates Foundation (BMGF), the Division of Intramural Research of the NIAID/NIH; and funding support from the Medicines for Malaria Venture and the NIH.
dc.description.urihttps://pubs.acs.org/journal/jmcmar?ref=breadcrumb
dc.identifier.citationDziwornu, G.A., Mmonwa, M.M., Coertzen, D. et al. 2025, 'Novel inhibitors of Plasmodium Phosphatidylinositol 4-kinase IIIβ with low propensity for resistance: life cycle stage activity and in vivo efficacy in a humanized mouse malaria infection model', Journal of Medicinal Chemistry, vol. 68, no. 16, pp. 17736–17751, doi : 10.1021/acs.jmedchem.5c01417.
dc.identifier.issn0022-2623 (print)
dc.identifier.issn1520-4804 (online)
dc.identifier.other10.1021/acs.jmedchem.5c01417
dc.identifier.urihttp://hdl.handle.net/2263/105327
dc.language.isoen
dc.publisherAmerican Chemical Society
dc.rights© 2025 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0 .
dc.subjectAssays
dc.subjectInhibition
dc.subjectParasites
dc.subjectPhotovoltaics
dc.subjectRodent models
dc.subjectAtaxia-telangiectasia-mutated (ATM)
dc.subjectArtemisinin-based combination therapy (ACT)
dc.subjectMalaria
dc.subjectSeasonal malaria chemoprevention (SMC)
dc.titleNovel inhibitors of Plasmodium Phosphatidylinositol 4-kinase IIIβ with low propensity for resistance : life cycle stage activity and in vivo efficacy in a humanized mouse malaria infection model
dc.typeArticle

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