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  • Synthesis, biological evaluation and mechanistic studies of totarol amino alcohol derivatives as potential antimalarial agents.

Synthesis, biological evaluation and mechanistic studies of totarol amino alcohol derivatives as potential antimalarial agents.

Bioorganic & medicinal chemistry (2011-12-27)
Claire Tacon, Eric M Guantai, Peter J Smith, Kelly Chibale
ABSTRACT

Herein we report on the semisynthesis and biological evaluation of β-amino alcohol derivatives of the natural product totarol and other simple aromatic systems. All β-amino alcohol derivatives of totarol exhibited higher antiplasmodial activity than totarol [IC(50): 11.69 μM (K1, chloroquine and multi-drug resistant strain), and 11.78 μM (D10, chloroquine sensitive strain)]-12e was the most active [IC(50): 0.63 μM (K1), and 0.61 μM (D10)]. The phenyl and naphthyl β-amino alcohol derivatives were much less active than their corresponding totarol equivalents. The majority of the β-amino alcohol derivatives of totarol were more active against K1 than the D10 strains of Plasmodium falciparum, a trend similar to the inverse relationship observed with the established aryl-amino alcohol antimalarial mefloquine. Selected compounds were shown to affect erythrocyte morphology, inhibit erythrocyte invasion and trigger CQ accumulation.

MATERIALS
Product Number
Brand
Product Description

Supelco
Phenol solution, certified reference material, 500 μg/mL in methanol
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Phenol solution, 5000 μg/mL in methanol, certified reference material
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Phenol, puriss., meets analytical specification of Ph. Eur., BP, USP, 99.5-100.5% (GC)
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Phenol solution, 100 μg/mL in acetonitrile, PESTANAL®, analytical standard
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2-Naphthol, 98%
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1,2-Epoxy-3-phenoxypropane, 99%