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

Bioorg Med Chem Lett. 2018 Oct 15;28(19):3168-3173. doi: 10.1016/j.bmcl.2018.08.028. Epub 2018 Aug 27.

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.

Keywords: Malaria; PfPKG; Plasmodium falciparum; Thiazole.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Cyclic GMP-Dependent Protein Kinases / antagonists & inhibitors*
  • Humans
  • Oxidation-Reduction
  • Plasmodium falciparum / enzymology*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Protozoan Proteins / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*

Substances

  • Antimalarials
  • Protein Kinase Inhibitors
  • Protozoan Proteins
  • Thiazoles
  • Cyclic GMP-Dependent Protein Kinases