AI Article Synopsis
- A series of hybrids combining 4-aminoquinoline and 3-hydroxypyridin-4-one was developed and tested against different strains of Plasmodium falciparum, a malaria-causing parasite.
- The synthesized compounds showed increased potency in inhibiting β-hematin formation compared to chloroquine, especially in CQ-resistant strains.
- Specific hybrids, including 8c, 8d, and 7g, demonstrated particularly strong antiplasmodial activity, with low micromolar concentrations required for effectiveness.
Article Abstract
A series of noncytotoxic 4-aminoquinoline-3-hydroxypyridin-4-one hybrids were synthesized on the basis of a synergistic in vitro combination of a precursor N-alkyl-3-hydroxypyridin-4-one with chloroquine (CQ) and tested in vitro against CQ resistant (K1 and W2) and sensitive (3D7) strains of Plasmodium falciparum. In vitro antiplasmodial activity of the precursors was negated by blocking the chelator moiety via complexation with gallium(III) or benzyl protection. None of the precursors inhibited β-hematin formation. Most hybrids were more potent inhibitors of β-hematin formation than CQ, and a correlation between antiplasmodial activity and inhibition of β-hematin formation was observed. Potent hybrids against K1, 3D7, and W2, respectively, were 8c (0.13, 0.004, and 0.1 μM); 8d (0.08, 0.01, and 0.02 μM); and 7g (0.07, 0.03, and 0.08 μM).
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4027233 | PMC |
| http://dx.doi.org/10.1021/ml4001084 | DOI Listing |
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