Evaluation of 4-Amino 2-Anilinoquinazolines against Plasmodium and Other Apicomplexan Parasites In Vitro and in a P. falciparum Humanized NOD-scid IL2R gamma(null) Mouse Model of Malaria
Paul R Gilson, William Nguyen, William A Poole, Jose E Teixeira, Jennifer K Thompson, Kaiyuan Guo, Rebecca J Stewart, Trent D Ashton, Karen L White, Laura M Sanz, Francisco-Javier Gamo, Susan A Charman, Sergio Wittlin, James Duffy, Christopher J Tonkin, Wai-Hong Tham, Brendan S Crabb, Brian M Cooke, Christopher D Huston, Alan F Cowman Show all
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | AMER SOC MICROBIOLOGY | Published : 2019
A series of 4-amino 2-anilinoquinazolines optimized for activity against the most lethal malaria parasite of humans, Plasmodium falciparum, was evaluated for activity against other human Plasmodium parasites and related apicomplexans that infect humans and animals. Four of the most promising compounds from the 4-amino 2-anilinoquinazoline series were equally as effective against the asexual blood stages of the zoonotic P. knowlesi, suggesting that they could also be effective against the closely related P. vivax, another important human pathogen. The 2-anilinoquinazoline compounds were also potent against an array of P. falciparum parasites resistant to clinically available antimalarial comp..View full abstract
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Awarded by National Health and Medical Research Council of Australia
Awarded by Australian Research Council
This work was funded by the National Health and Medical Research Council of Australia (development grant 1113712 to B.E.S. and program grant 1092789 to A.F.C.), the Australian Research Council (to B.M.C.), The International Development Research Centre Canada (to B.M.C.), the Australian Cancer Research Foundation, the Victorian State Government Operational Infrastructure Support, and Australian Government NHMRC IRI-ISS. C.J.T. is an Australian Research Council Future Fellow (FT120100164), B.E.S. is a Corin Centenary Fellow, and A.F.C. is a Howard Hughes International Scholar.