Identification of Plasmodium falciparum heat shock 90 inhibitors via molecular docking

Bioorg Med Chem Lett. 2021 Mar 1:35:127818. doi: 10.1016/j.bmcl.2021.127818. Epub 2021 Jan 26.


A virtual screen was performed to identify anti-malarial compounds targeting Plasmodium falciparum heat shock 90 protein by applying a series of drug-like and commercial availability filters to compounds in the ZINC database, resulting in a virtual library of more than 13 million candidates. The goal of the virtual screen was to identify novel compounds which could serve as a starting point for the development of antimalarials with a mode of action different from anything currently used in the clinic. The screen targeted the ATP binding pocket of the highly conserved Plasmodium heat shock 90 protein, as this protein is critical to the survival of the parasite and has several significant structural differences from the human homolog. The top twelve compounds from the virtual screen were tested in vitro, with all twelve showing no antiproliferative activity against the human fibroblast cell line and three compounds exhibiting single digit or better micromolar antiproliferative activity against the chloroquine-sensitive P. falciparum 3D7 strain.

Keywords: Antimalarial drugs; Molecular docking; PfHsp90 inhibitors; Structure based docking; Virtual screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Cell Line
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Fibroblasts / drug effects
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • HSP90 Heat-Shock Proteins / metabolism
  • Humans
  • Molecular Docking Simulation*
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / metabolism
  • Structure-Activity Relationship


  • Antimalarials
  • HSP90 Heat-Shock Proteins