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 language | English (US) |
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Pages (from-to) | 1611-1620 |
Number of pages | 10 |
Journal | Future Medicinal Chemistry |
Volume | 14 |
Issue number | 22 |
DOIs | |
State | Published - 2022 |
Keywords
- 2-hydroxy-1,4-naphthoquinones
- Plasmodium falciparum
- malaria
- radical alkylation
- three-component reductive alkylation
ASJC Scopus subject areas
- Molecular Medicine
- Pharmacology
- Drug Discovery