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

In 1948, the synthesis and activity of 2-hydroxy-1,4-naphthoquinones containing 3-alkyldiarylether side chains was reported. The synthesis of five related compounds, designed to be more metabolically stable, was pursued. The compounds were synthesized using a radical alkylation reaction with naphtho...

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Published in:Future medicinal chemistry 2022-11, Vol.14 (22), p.1611-1620
Main Authors: Berg, Amanda, Swartchick, Chelsea B, Forrest, Noah, Chavarria, Matthew, Deem, Madeleine C, Sillin, Alyson N, Li, Yuexin, Riscoe, Teresa M, Nilsen, Aaron, Riscoe, Michael K, Wood, Warren Jl
Format: Article
Language:English
Subjects:
Antimalarials - chemistry
Humans
Naphthoquinones
Plasmodium falciparum
Short Communication
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Summary:In 1948, the synthesis and activity of 2-hydroxy-1,4-naphthoquinones containing 3-alkyldiarylether side chains was reported. 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 IC value against various strains of and assay data indicate that it binds to the Q site of cytochrome bc . With a low yield for the radical alkylation of the most active compound, a reductive alkylation method with used to improve reaction yields. Further synthetic knowledge was obtained, and the assay data indicate that there are sensitivity differences between avian and human malarial parasites for these molecules.
ISSN:1756-8919
1756-8927
DOI:10.4155/fmc-2022-0127