Trisubstituted thiazoles as potent and selective inhibitors of Plasmodium falciparum protein kinase G (PfPKG).

Tsagris, Denise J; Birchall, Kristian; Bouloc, Nathalie; Large, Jonathan M; Merritt, Andy; Smiljanic-Hurley, Ela; Wheldon, Mary; Ansell, Keith H; Kettleborough, Catherine; Whalley, David; +4 more... Stewart, Lindsay B; Bowyer, Paul W; Baker, David A; Osborne, Simon A; (2018) Trisubstituted thiazoles as potent and selective inhibitors of Plasmodium falciparum protein kinase G (PfPKG). Bioorganic & medicinal chemistry letters, 28 (19). pp. 3168-3173. ISSN 0960-894X DOI: https://doi.org/10.1016/j.bmcl.2018.08.028

Abstract

A series of trisubstituted thiazoles have been identified as potent inhibitors of Plasmodium falciparum (Pf) cGMP-dependent protein kinase (PfPKG) through template hopping from known Eimeria PKG (EtPKG) inhibitors. The thiazole series has yielded compounds with improved potency, kinase selectivity and good in vitro ADME properties. These compounds could be useful tools in the development of new anti-malarial drugs in the fight against drug resistant malaria.

Additional Information

Item Type	Article
Faculty and Department	Faculty of Infectious and Tropical Diseases > Department of Infection Biology
Research Centre	Malaria Centre Antimicrobial Resistance Centre (AMR)
PubMed ID	30174152
Related URLs	OA Location