teriflunomide and Malaria--Falciparum

teriflunomide has been researched along with Malaria--Falciparum* in 4 studies

Other Studies

4 other study(ies) available for teriflunomide and Malaria--Falciparum

ArticleYear
Lead Optimization of a Pyrrole-Based Dihydroorotate Dehydrogenase Inhibitor Series for the Treatment of Malaria.
    Journal of medicinal chemistry, 2020, 05-14, Volume: 63, Issue:9

    Malaria puts at risk nearly half the world's population and causes high mortality in sub-Saharan Africa, while drug resistance threatens current therapies. The pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (DHODH) is a validated target for malaria treatment based on our finding that triazolopyrimidine DSM265 (

    Topics: Animals; Antimalarials; Cell Line, Tumor; Crystallography, X-Ray; Dihydroorotate Dehydrogenase; Dogs; Enzyme Inhibitors; Female; Humans; Malaria, Falciparum; Male; Mice, SCID; Microsomes, Liver; Molecular Structure; Oxidoreductases Acting on CH-CH Group Donors; Parasitic Sensitivity Tests; Plasmodium falciparum; Plasmodium vivax; Protein Binding; Pyrroles; Rats; Structure-Activity Relationship

2020
A High-Throughput Assay to Identify Inhibitors of the Apicoplast DNA Polymerase from Plasmodium falciparum.
    Journal of biomolecular screening, 2014, Volume: 19, Issue:6

    Infection by Plasmodium falciparum is the leading cause of malaria in humans. The parasite contains a unique and essential plastid-like organelle called the apicoplast that, similar to the mitochondria and chloroplast, houses its own genome that must undergo replication and repair. The putative apicoplast replicative DNA polymerase, POM1, has no direct orthologs in mammals, making the P. falciparum POM1 an attractive antimalarial drug target. Here, we report on a fluorescent high-throughput DNA polymerase assay that relies on the ability of POM1 to perform strand-displacement synthesis through the stem of a DNA hairpin substrate, thereby separating a Cy3 dye from a quencher. Assay-validation experiments were performed using 384-well plates and resulted in a signal window of 7.90 and aZ' factor of 0.71. A pilot screen of a 2880-compound library identified 62 possible inhibitors that cause more than 50% inhibition of polymerase activity. The simplicity and statistical robustness of the assay suggest it is well suited for the screening of novel apicoplast polymerase inhibitors that may serve as lead compounds in antimalarial drug-discovery efforts.

    Topics: Antimalarials; Apicoplasts; Chloroplasts; DNA; DNA-Directed DNA Polymerase; Drug Discovery; Exonucleases; Humans; Kinetics; Malaria, Falciparum; Mitochondria; Multienzyme Complexes; Nucleic Acid Synthesis Inhibitors; Peptide Library; Plasmodium falciparum; Protozoan Proteins; Spectrometry, Fluorescence

2014
Novel selective and potent inhibitors of malaria parasite dihydroorotate dehydrogenase: discovery and optimization of dihydrothiophenone derivatives.
    Journal of medicinal chemistry, 2013, Oct-24, Volume: 56, Issue:20

    Taking the emergence of drug resistance and lack of effective antimalarial vaccines into consideration, it is of significant importance to develop novel antimalarial agents for the treatment of malaria. Herein, we elucidated the discovery and structure-activity relationships of a series of dihydrothiophenone derivatives as novel specific inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH). The most promising compound, 50, selectively inhibited PfDHODH (IC50 = 6 nM, with >14,000-fold species-selectivity over hDHODH) and parasite growth in vitro (IC50 = 15 and 18 nM against 3D7 and Dd2 cells, respectively). Moreover, an oral bioavailability of 40% for compound 50 was determined from in vivo pharmacokinetic studies. These results further indicate that PfDHODH is an effective target for antimalarial chemotherapy, and the novel scaffolds reported in this work might lead to the discovery of new antimalarial agents.

    Topics: 2-Naphthylamine; Animals; Antimalarials; Area Under Curve; Dihydroorotate Dehydrogenase; Drug Discovery; Enzyme Inhibitors; Furans; Host-Parasite Interactions; Humans; Malaria, Falciparum; Male; Models, Chemical; Molecular Structure; Oxidoreductases Acting on CH-CH Group Donors; Plasmodium falciparum; Protozoan Proteins; Rats; Rats, Sprague-Dawley

2013
Addressing the malaria drug resistance challenge using flow cytometry to discover new antimalarials.
    Bioorganic & medicinal chemistry letters, 2009, Sep-15, Volume: 19, Issue:18

    A new flow cytometry method that uses an optimized DNA and RNA staining strategy to monitor the growth and development of the Plasmodium falciparum strain W2mef has been used in a pilot study and has identified Bay 43-9006 1, SU 11274 2, and TMC 125 5 as compounds that exhibit potent (<1 microM) overall and ring stage in vitro antimalarial activity.

    Topics: Animals; Antimalarials; DNA, Protozoan; Drug Discovery; Drug Resistance; Erythrocytes; Flow Cytometry; Malaria, Falciparum; Parasitic Sensitivity Tests; Plasmodium falciparum; RNA, Protozoan; Structure-Activity Relationship

2009