• myGriffith
    • Staff portal
    • Contact Us⌄
      • Future student enquiries 1800 677 728
      • Current student enquiries 1800 154 055
      • International enquiries +61 7 3735 6425
      • General enquiries 07 3735 7111
      • Online enquiries
      • Staff phonebook
    View Item 
    •   Home
    • Griffith Research Online
    • Journal articles
    • View Item
    • Home
    • Griffith Research Online
    • Journal articles
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

  • All of Griffith Research Online
    • Communities & Collections
    • Authors
    • By Issue Date
    • Titles
  • This Collection
    • Authors
    • By Issue Date
    • Titles
  • Statistics

  • Most Popular Items
  • Statistics by Country
  • Most Popular Authors
  • Support

  • Contact us
  • FAQs
  • Admin login

  • Login
  • 3,3 '-Disubstituted 5,5 '-Bi(1,2,4-triazine) Derivatives with Potent in Vitro and in Vivo Antimalarial Activity

    Author(s)
    Xue, Lian
    Shi, Da-Hua
    Harjani, Jitendra R
    Huang, Fei
    Beveridge, Julia G
    Dingjan, Tamir
    Ban, Kung
    Diab, Sarah
    Duffy, Sandra
    Lucantoni, Leonardo
    Fletcher, Sabine
    Chiu, Francis CK
    Blundell, Scott
    Ellis, Katherine
    Ralph, Stuart A
    Wirjanata, Grennady
    Teguh, Silvia
    Noviyanti, Rintis
    Chavchich, Marina
    Creek, Darren
    Price, Ric N
    Marfurt, Jutta
    Charman, Susan A
    Cuellar, Matthew E
    Strasser, Jessica M
    Dahlin, Jayme L
    Walters, Michael A
    Edstein, Michael D
    Avery, Vicky M
    Baell, Jonathan B
    Griffith University Author(s)
    Duffy, Sandra
    Avery, Vicky M.
    Year published
    2019
    Metadata
    Show full item record
    Abstract
    A series of 3,3′-disubstituted 5,5′-bi(1,2,4-triazine) derivatives was synthesized and screened against the erythrocytic stage of Plasmodium falciparum 3D7 line. The most potent dimer, 6k, with an IC50 (50% inhibitory concentration) of 0.008 μM, had high in vitro potency against P. falciparum lines resistant to chloroquine (W2, IC50 = 0.0047 ± 0.0011 μM) and artemisinin (MRA1240, IC50 = 0.0086 ± 0.0010 μM). Excellent ex vivo potency of 6k was shown against clinical field isolates of both P. falciparum (IC50 = 0.022–0.034 μM) and Plasmodium vivax (IC50 = 0.0093–0.031 μM) from the blood of outpatients with uncomplicated malaria. ...
    View more >
    A series of 3,3′-disubstituted 5,5′-bi(1,2,4-triazine) derivatives was synthesized and screened against the erythrocytic stage of Plasmodium falciparum 3D7 line. The most potent dimer, 6k, with an IC50 (50% inhibitory concentration) of 0.008 μM, had high in vitro potency against P. falciparum lines resistant to chloroquine (W2, IC50 = 0.0047 ± 0.0011 μM) and artemisinin (MRA1240, IC50 = 0.0086 ± 0.0010 μM). Excellent ex vivo potency of 6k was shown against clinical field isolates of both P. falciparum (IC50 = 0.022–0.034 μM) and Plasmodium vivax (IC50 = 0.0093–0.031 μM) from the blood of outpatients with uncomplicated malaria. Despite 6k being cleared relatively rapidly in mice, it suppressed parasitemia in the Peters 4-day test, with a mean ED50 value (50% effective dose) of 1.47 mg kg–1 day–1 following oral administration. The disubstituted triazine dimer 6k represents a new class of orally available antimalarial compounds of considerable interest for further development.
    View less >
    Journal Title
    Journal of Medicinal Chemistry
    Volume
    62
    Issue
    5
    DOI
    https://doi.org/10.1021/acs.jmedchem.8b01799
    Subject
    Medicinal and biomolecular chemistry
    Organic chemistry
    Pharmacology and pharmaceutical sciences
    Science & Technology
    Life Sciences & Biomedicine
    Chemistry, Medicinal
    Pharmacology & Pharmacy
    PLASMODIUM-FALCIPARUM
    Publication URI
    http://hdl.handle.net/10072/386725
    Collection
    • Journal articles

    Footer

    Disclaimer

    • Privacy policy
    • Copyright matters
    • CRICOS Provider - 00233E
    • TEQSA: PRV12076

    Tagline

    • Gold Coast
    • Logan
    • Brisbane - Queensland, Australia
    First Peoples of Australia
    • Aboriginal
    • Torres Strait Islander