In vitro antimalarial activity of hyperforin, a prenylated acylphloroglucinol. A structure–activity study

The antimalarial activity of hyperforin, a phenol-like compound that can be easily absorbed orally, and a series of derivatives variously modified on the cyclohexatrienone system was investigated. Hyperforin was active against Plasmodium falciparum with an IC50 value in the micromolar range, and the activity was not critically dependent on either its phenol-like sensitivity to autooxidation or the presence of unsaturation on the prenyl residues. Related phloroglucinols like the hop β-acids and the enantiomers of usnic acid showed only marginal activity, suggesting that hyperforin is a new antimalarial chemotype.

Graphical abstractThe antimalarial activity of hyperforin and a series of derivatives variously modified on the cyclohexatrienone system was investigated. Hyperforin was active against Plasmodium falciparum with an IC50 value in the micromolar range, and the activity was not critically dependent on either its phenol-like sensitivity to autooxidation or the presence of unsaturation on the prenyl residues.Figure optionsDownload full-size imageDownload as PowerPoint slide