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

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.

Document Details

Document Type
Pub Defense Publication
Publication Date
Nov 01, 2022
Source ID
10.4155/fmc-2022-0127

Entities

People

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

Organizations

  • M J Murdock Charitable Trust
  • National Institute of Allergy and Infectious Diseases
  • Oregon Health & Science University
  • United States Department of Defense
  • United States Department of Veterans Affairs
  • University of Portland
  • Veterans Affairs Medical Center (Oregon)

Tags

Fields of Study

  • Chemistry

Readers

  • Organic Chemistry
  • Parasitology and Pharmacology of Malaria.
  • Seismology