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antimalarial agents

  • Open Access
    Defining the Antimalarial Activity of Cipargamin in Healthy Volunteers Experimentally Infected with Blood-Stage <span class="named-content genus-species" id="named-content-1">Plasmodium falciparum</span>
    Clinical Therapeutics
    Defining the Antimalarial Activity of Cipargamin in Healthy Volunteers Experimentally Infected with Blood-Stage Plasmodium falciparum

    The spiroindolone cipargamin, a new antimalarial compound that inhibits Plasmodium ATP4, is currently in clinical development. This study aimed to characterize the antimalarial activity of cipargamin in healthy volunteers experimentally infected with blood-stage Plasmodium falciparum.

    James S. McCarthy, Azrin N. Abd-Rahman, Katharine A. Collins, Louise Marquart, Paul Griffin, Anne Kümmel, Aline Fuchs, Cornelis Winnips, Vishal Mishra, Katalin Csermak-Renner, J. Prakash Jain, Preetam Gandhi
  • Open Access
    <em>In Vivo</em> Efficacy and Metabolism of the Antimalarial Cycleanine and Improved <em>In Vitro</em> Antiplasmodial Activity of Semisynthetic Analogues
    Pharmacology
    In Vivo Efficacy and Metabolism of the Antimalarial Cycleanine and Improved In Vitro Antiplasmodial Activity of Semisynthetic Analogues

    Bisbenzylisoquinoline (BBIQ) alkaloids are a diverse group of natural products that demonstrate a range of biological activities. In this study, the in vitro antiplasmodial activity of three BBIQ alkaloids (cycleanine [compound 1], isochondodendrine [compound 2], and 2′-norcocsuline [compound 3]) isolated from the Triclisia subcordata Oliv. medicinal plant...

    Fidelia Ijeoma Uche, Xiaozhen Guo, Jude Okokon, Imran Ullah, Paul Horrocks, Joshua Boateng, Chenggang Huang, Wen-Wu Li
  • Regioisomerization of Antimalarial Drug WR99210 Explains the Inactivity of a Commercial Stock
    Chemistry; Biosynthesis
    Regioisomerization of Antimalarial Drug WR99210 Explains the Inactivity of a Commercial Stock

    WR99210, a former antimalarial drug candidate now widely used for the selection of Plasmodium transfectants, selectively targets the parasite’s dihydrofolate reductase thymidine synthase bifunctional enzyme (DHFR-TS) but not human DHFR, which is not fused with TS. Accordingly, WR99210 and plasmids expressing the human dhfr gene have become valued tools for the genetic modification of parasites in the laboratory....

    T. Parks Remcho, Sravanthi D. Guggilapu, Phillip Cruz, Glenn A. Nardone, Gavin Heffernan, Robert D. O’Connor, Carole A. Bewley, Thomas E. Wellems, Kristin D. Lane
  • Open Access
    Tolerance of Gambian <span class="named-content genus-species" id="named-content-1">Plasmodium falciparum</span> to Dihydroartemisinin and Lumefantrine Detected by <em>Ex Vivo</em> Parasite Survival Rate Assay
    Susceptibility
    Tolerance of Gambian Plasmodium falciparum to Dihydroartemisinin and Lumefantrine Detected by Ex Vivo Parasite Survival Rate Assay

    Monitoring of Plasmodium falciparum sensitivity to antimalarial drugs in Africa is vital for malaria elimination. However, the commonly used ex vivo/in vitro 50% inhibitory concentration (IC50) test gives inconsistent results for several antimalarials, while the alternative ring-stage survival assay (RSA) for artemisinin derivatives has...

    Haddijatou Mbye, Fatoumata Bojang, Aminata Seedy Jawara, Bekai Njie, Nuredin Ibrahim Mohammed, Joseph Okebe, Umberto D’Alessandro, Alfred Amambua-Ngwa
  • <span class="named-content genus-species" id="named-content-1">Plasmodium falciparum</span> Isolates Carrying <em>pf</em>k13 Polymorphisms Harbor the SVMNT Allele of <em>pfcrt</em> in Northwestern Indonesia
    Mechanisms of Resistance
    Plasmodium falciparum Isolates Carrying pfk13 Polymorphisms Harbor the SVMNT Allele of pfcrt in Northwestern Indonesia

    Artemisinin-based combination therapy (ACT) is the first-line antimalarial regimen in Indonesia. Susceptibility of Plasmodium falciparum to artemisinin is falling in the Greater Mekong subregion, but it is not known whether the efficacy of current combinations is also threatened in nearby Sumatera. We evaluated the genetic loci pfcrt, pfmdr1, and pfk13...

    Inke N. D. Lubis, Hendri Wijaya, Munar Lubis, Chairuddin P. Lubis, Khalid B. Beshir, Colin J. Sutherland
  • Activity of Epigenetic Inhibitors against <span class="named-content genus-species" id="named-content-1">Plasmodium falciparum</span> Asexual and Sexual Blood Stages
    Susceptibility
    Activity of Epigenetic Inhibitors against Plasmodium falciparum Asexual and Sexual Blood Stages

    Earlier genetic and inhibitor studies showed that epigenetic regulation of gene expression is critical for malaria parasite survival in multiple life stages and a promising target for new antimalarials. We therefore evaluated the activity of 350 diverse epigenetic inhibitors against multiple stages of Plasmodium falciparum. We observed ≥90% inhibition at 10 μM for 28...

    Leen N. Vanheer, Hao Zhang, Gang Lin, Björn F. C. Kafsack
  • Open Access
    Pooled Multicenter Analysis of Cardiovascular Safety and Population Pharmacokinetic Properties of Piperaquine in African Patients with Uncomplicated Falciparum Malaria
    Clinical Therapeutics
    Pooled Multicenter Analysis of Cardiovascular Safety and Population Pharmacokinetic Properties of Piperaquine in African Patients with Uncomplicated Falciparum Malaria

    Dihydroartemisinin-piperaquine has shown excellent efficacy and tolerability in malaria treatment. However, concerns have been raised of potentially harmful cardiotoxic effects associated with piperaquine. The population pharmacokinetics and cardiac effects of piperaquine were evaluated in 1,000 patients, mostly children enrolled in a multicenter trial from 10 sites in Africa. A linear relationship described the QTc-prolonging effect of...

    Thanaporn Wattanakul, Bernhards Ogutu, Abdunoor M. Kabanywanyi, Kwaku-Poku Asante, Abraham Oduro, Alex Adjei, Ali Sie, Esperanca Sevene, Eusebio Macete, Guillaume Compaore, Innocent Valea, Isaac Osei, Markus Winterberg, Margaret Gyapong, Martin Adjuik, Salim Abdulla, Seth Owusu-Agyei, Nicholas J. White, Nicholas P. J. Day, Halidou Tinto, Rita Baiden, Fred Binka, Joel Tarning
  • Open Access
    A Randomized Controlled Trial of Three- versus Five-Day Artemether-Lumefantrine Regimens for Treatment of Uncomplicated <span class="named-content genus-species" id="named-content-1">Plasmodium falciparum</span> Malaria in Pregnancy in Africa
    Clinical Therapeutics
    A Randomized Controlled Trial of Three- versus Five-Day Artemether-Lumefantrine Regimens for Treatment of Uncomplicated Plasmodium falciparum Malaria in Pregnancy in Africa

    Artemether-lumefantrine antimalarial efficacy in pregnancy could be compromised by reduced drug exposure. Population-based simulations suggested that therapeutic efficacy would be improved if the treatment duration was increased.

    Marie A. Onyamboko, Richard M. Hoglund, Sue J. Lee, Charlie Kabedi, Daddy Kayembe, Benjamin B. Badjanga, Gareth D. H. Turner, Nikky V. Jackson, Joel Tarning, Rose McGready, Francois Nosten, Nicholas J. White, Nicholas P. J. Day, Caterina Fanello
  • Modification of <em>pfap2μ</em> and <em>pfubp1</em> Markedly Reduces Ring-Stage Susceptibility of <span class="named-content genus-species" id="named-content-1">Plasmodium falciparum</span> to Artemisinin <em>In Vitro</em>
    Mechanisms of Resistance
    Modification of pfap2μ and pfubp1 Markedly Reduces Ring-Stage Susceptibility of Plasmodium falciparum to Artemisinin In Vitro

    Management of uncomplicated malaria worldwide is threatened by the emergence in Asia of Plasmodium falciparum carrying variants of the pfk13 locus and exhibiting reduced susceptibility to artemisinin. Mutations in two other genes, ubp1 and ap2μ, are associated with artemisinin resistance in rodent malaria and with clinical failure of...

    Ryan C. Henrici, Donelly A. van Schalkwyk, Colin J. Sutherland
  • Efficacy and Safety of Pyronaridine-Artesunate plus Single-Dose Primaquine for the Treatment of Malaria in Western Cambodia
    Clinical Therapeutics
    Efficacy and Safety of Pyronaridine-Artesunate plus Single-Dose Primaquine for the Treatment of Malaria in Western Cambodia

    This single-arm trial (n = 104) in western Cambodia showed high efficacy for 3-day treatment with pyronaridine-artesunate plus single-dose primaquine in Plasmodium falciparum malaria.

    Rithea Leang, Nimol Khim, Huch Chea, Rekol Huy, Melissa Mairet-Khedim, Denis Mey Bouth, Maria Dorina Bustos, Pascal Ringwald, Benoit Witkowski

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