Inhibitors of the Plasmodium falciparum Hsp90 towards Selective Antimalarial Drug Design: The Past, Present and Future

Cells. 2021 Oct 22;10(11):2849. doi: 10.3390/cells10112849.

Abstract

Malaria is still one of the major killer parasitic diseases in tropical settings, posing a public health threat. The development of antimalarial drug resistance is reversing the gains made in attempts to control the disease. The parasite leads a complex life cycle that has adapted to outwit almost all known antimalarial drugs to date, including the first line of treatment, artesunate. There is a high unmet need to develop new strategies and identify novel therapeutics to reverse antimalarial drug resistance development. Among the strategies, here we focus and discuss the merits of the development of antimalarials targeting the Heat shock protein 90 (Hsp90) due to the central role it plays in protein quality control.

Keywords: Hsp90 inhibitors; Plasmodium falciparum; heat shock protein 90; malaria; molecular chaperone; parasite Hsp90.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Drug Design*
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • HSP90 Heat-Shock Proteins / chemistry
  • HSP90 Heat-Shock Proteins / metabolism
  • Humans
  • Plasmodium falciparum / metabolism*

Substances

  • Antimalarials
  • HSP90 Heat-Shock Proteins