Investigating Sulfoxide-to-Sulfone Conversion as a Prodrug Strategy for a Phosphatidylinositol 4-Kinase Inhibitor in a Humanized Mouse Model of Malaria | Zendy

Liezl Gibhard | Zendy; Mathew Njoroge | Zendy; Tanya Paquet | Zendy; Christel Brunschwig | Zendy; Dale Taylor | Zendy; Nina Lawrence | Zendy; Efrem Abay | Zendy; Sergio Wittlin | Zendy; Lubbe Wiesner | Zendy; Leslie J. Street | Zendy; Kelly Chibale | Zendy; Gregory S. Basarab | Zendy

Open Access

Investigating Sulfoxide-to-Sulfone Conversion as a Prodrug Strategy for a Phosphatidylinositol 4-Kinase Inhibitor in a Humanized Mouse Model of Malaria

Author(s) -

Liezl Gibhard,

Mathew Njoroge,

Tanya Paquet,

Christel Brunschwig,

Dale Taylor,

Nina Lawrence,

Efrem Abay,

Sergio Wittlin,

Lubbe Wiesner,

Leslie J. Street,

Kelly Chibale,

Gregory S. Basarab

Publication year - 2018

Publication title -

antimicrobial agents and chemotherapy

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.07

H-Index - 259

eISSN - 1070-6283

pISSN - 0066-4804

DOI - 10.1128/aac.00261-18

Subject(s) - prodrug , sulfone , pharmacology , plasmodium falciparum , metabolite , in vivo , plasmodium vivax , malaria , biology , phosphatidylinositol , kinase , chemistry , biochemistry , immunology , microbiology and biotechnology , polymer chemistry

Thein vivo antimalarial efficacies of two phosphatidylinositol 4-kinase (PI4K) inhibitors, a 3,5-diaryl-2-aminopyrazine sulfoxide and its corresponding sulfone metabolite, were evaluated in the NOD-scid IL2Rγnull (NSG) murine malaria disease model ofPlasmodium falciparum infection. We hypothesized that the sulfoxide would serve as a more soluble prodrug for the sulfone, which would lead to improved drug exposure with oral dosing.

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