Identification of Plasmodium falciparum heat shock 90 inhibitors via molecular docking

Nikalet Everson, Jordan Bach, Jared T. Hammill, Mofolusho O. Falade, Amy L. Rice, R. Kiplin Guy, Scott Eagon

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish
Article number127818
JournalBioorganic and Medicinal Chemistry Letters
Volume35
DOIs
StatePublished - Mar 1 2021

Bibliographical note

Funding Information:
This research was supported by the Bill and Linda Frost Fund at California Polytechnic State University .

Funding Information:
This research was supported by the Bill and Linda Frost Fund at California Polytechnic State University.

Publisher Copyright:
© 2021 The Author(s)

Keywords

  • Antimalarial drugs
  • Molecular docking
  • PfHsp90 inhibitors
  • Structure based docking
  • Virtual screening

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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