Antimalarial activity of 2,6-dibenzylidenecyclohexanone derivatives

Bioorg Med Chem Lett. 2021 Sep 1:47:128216. doi: 10.1016/j.bmcl.2021.128216. Epub 2021 Jun 19.


Malaria remains one of the deadliest infectious diseases worldwide and continues to infect hundreds of millions of individuals each year. Here we report the discovery and derivatization of a series of 2,6-dibenzylidenecyclohexanones targeting the chloroquine-sensitive 3D7 strain of Plasmodium falciparum . While the initial lead compound displayed significant toxicity in a human cell proliferation assay, we were able to identify a derivative with no detectable toxicity and sub-micromolar potency.

Keywords: 2,6-Dibenzylidenecyclohexanone; Malaria; Michael system; Plasmodium falciparum; Structure activity relationship.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimalarials / chemical synthesis
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Cell Proliferation / drug effects
  • Chloroquine / chemical synthesis
  • Chloroquine / chemistry
  • Chloroquine / pharmacology*
  • Dose-Response Relationship, Drug
  • Fibroblasts / drug effects
  • Humans
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Plasmodium falciparum / drug effects*
  • Structure-Activity Relationship


  • Antimalarials
  • Chloroquine