2-hydroxy-1,4-naphthoquinones with 3-alkyldiarylether groups: synthesis and Plasmodium falciparum inhibitory activity

Amanda Berg, Chelsea B. Swartchick, Noah Forrest, Matthew Chavarria, Madeleine C. Deem, Alyson N. Sillin, Yuexin Li, Teresa M. Riscoe, Aaron Nilsen, Michael K. Riscoe, Warren Jl Wood

Research output: Contribution to journalArticlepeer-review

Abstract

Background: In 1948, the synthesis and Plasmodium lophurae activity of 2-hydroxy-1,4-naphthoquinones containing 3-alkyldiarylether side chains was reported. Method/results: The synthesis of five related compounds, designed to be more metabolically stable, was pursued. The compounds were synthesized using a radical alkylation reaction with naphthoquinones. One compound had a lower IC50 value against various strains of Plasmodium falciparum and assay data indicate that it binds to the Qo site of cytochrome bc1. With a low yield for the radical alkylation of the most active compound, a reductive alkylation method with used to improve reaction yields. Conclusion: Further synthetic knowledge was obtained, and the assay data indicate that there are sensitivity differences between avian and human malarial parasites for these molecules.

Original languageEnglish (US)
Pages (from-to)1611-1620
Number of pages10
JournalFuture Medicinal Chemistry
Volume14
Issue number22
DOIs
StatePublished - Nov 1 2022

Keywords

  • 2-hydroxy-1,4-naphthoquinones
  • malaria
  • Plasmodium falciparum
  • radical alkylation
  • three-component reductive alkylation

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

Fingerprint

Dive into the research topics of '2-hydroxy-1,4-naphthoquinones with 3-alkyldiarylether groups: synthesis and Plasmodium falciparum inhibitory activity'. Together they form a unique fingerprint.

Cite this