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Abstract
The previously unknown antiplasmodial activity of the plant derived natural product totarol is reported. Novel β-amino alcohol derivatives based on this natural product were designed, synthesised and evaluated for in vitro antiplasmodial activity and cytotoxicity. These derivatives showed antiplasmodial IC 50 values in the range of 0.6–3.0 μM and were equally active against a chloroquine-sensitive and resistant strain of Plasmodium falciparum, while showing little cytotoxicity against a mammalian cell line (CHO). In terms of lead development, two of the compounds based on substituted phenylpiperazine warrant further investigation as potential antiplasmodial leads. In addition to their selective antiplasmodial activity and lack of chloroquine cross-resistance, these compounds are structurally different to any of the available antimalarial drugs.
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