Evaluation of 4-amino 2-anilinoquinazolines against Plasmodium and other apicomplexan parasites in vitro and in a P. falciparum humanized NOD-scid IL2R γnull mouse model of malaria.

Evaluation of 4-amino 2-anilinoquinazolines against Plasmodium and other apicomplexan parasites in vitro and in a P. falciparum humanized NOD-scid IL2Rγnull mouse model of malaria. Antimicrob Agents Chemother. 2018 Dec 17;: Authors: Gilson PR, Nguyen W, Poole WA, Teixeira JE, Thompson JK, Guo K, Stewart RJ, Ashton TD, White KL, Sanz LM, Gamo FJ, Charman SA, Wittlin S, Duffy J, Tonkin CJ, Tham WH, Crabb BS, Cooke BM, Huston CD, Cowman AF, Sleebs BE Abstract A series of 4-amino 2-anilinoquinazolines optimized for activity against the most lethal malaria parasite of humans, Plasmodium falciparum, were 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 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 anti-malarial compounds although slightly less so than the drug sensitive 3D7 parasite line. The apicomplexan parasites Toxoplasma gondii, Babesia bovis and Cryptosporidium parvum were less sensitive to the 2-anilinoquinazoline series with an EC50 generally in the low micromolar range suggesting the yet to be discov...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research