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• W2330496812 abstract "Despite significant advances in antimalarial chemotherapy over the past 30 years, development of resistance to frontline drugs remains a significant challenge that limits efforts to eradicate the disease. We now report the discovery of a new class of antimalarials, salinipostins A–K, with low nanomolar potencies and high selectivity indices against mammalian cells (salinipostin A: Plasmodium falciparum EC50 50 nM, HEK293T cytotoxicity EC50 > 50 μM). These compounds were isolated from a marine-derived Salinospora sp. bacterium and contain a bicyclic phosphotriester core structure, which is a rare motif among natural products. This scaffold differs significantly from the structures of known antimalarial compounds and represents a new lead structure for the development of therapeutic targets in malaria. Examination of the growth stage specificity of salinipostin A indicates that it exhibits growth stage-specific effects that differ from compounds that inhibit heme polymerization, while resistance selection experiments were unable to identify parasite populations that exhibited significant resistance against this compound class." @default.
• W2330496812 created "2016-06-24" @default.
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• W2330496812 date "2015-01-13" @default.
• W2330496812 modified "2023-10-13" @default.
• W2330496812 title "Salinipostins A–K, Long-Chain Bicyclic Phosphotriesters as a Potent and Selective Antimalarial Chemotype" @default.
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• W2330496812 doi "https://doi.org/10.1021/jo5024409" @default.
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• W2330496812 hasPublicationYear "2015" @default.
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