An Update on Development of Small-Molecule Plasmodial Kinase Inhibitors

Molecules. 2020 Nov 7;25(21):5182. doi: 10.3390/molecules25215182.

Abstract

Malaria control relies heavily on the small number of existing antimalarial drugs. However, recurring antimalarial drug resistance necessitates the continual generation of new antimalarial drugs with novel modes of action. In order to shift the focus from only controlling this disease towards elimination and eradication, next-generation antimalarial agents need to address the gaps in the malaria drug arsenal. This includes developing drugs for chemoprotection, treating severe malaria and blocking transmission. Plasmodial kinases are promising targets for next-generation antimalarial drug development as they mediate critical cellular processes and some are active across multiple stages of the parasite's life cycle. This review gives an update on the progress made thus far with regards to plasmodial kinase small-molecule inhibitor development.

Keywords: Plasmodium; antimalarial agents; kinase inhibitors; kinases; malaria.

Publication types

  • Review

MeSH terms

  • Animals
  • Antimalarials / pharmacology*
  • Calcium / metabolism
  • Casein Kinase I / metabolism
  • Culicidae
  • Drug Design
  • Drug Discovery / trends*
  • Drug Resistance
  • Glycogen Synthase Kinase 3 / metabolism
  • Humans
  • Imidazoles / pharmacology
  • Inhibitory Concentration 50
  • Life Cycle Stages / drug effects
  • MAP Kinase Signaling System
  • Malaria / drug therapy*
  • Phosphotransferases / chemistry
  • Plasmodium / drug effects*
  • Plasmodium / enzymology
  • Protein Kinase Inhibitors / pharmacology*
  • Pyridines / pharmacology

Substances

  • Antimalarials
  • Imidazoles
  • Protein Kinase Inhibitors
  • Pyridines
  • imidazopyridine
  • Phosphotransferases
  • Casein Kinase I
  • Glycogen Synthase Kinase 3
  • Calcium