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 IC(50) 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 beta-acids and the enantiomers of usnic acid showed only marginal activity, suggesting that hyperforin is a new antimalarial chemotype.
Verotta
Luisella
L
Dipartimento di Chimica Organica e Industriale, Via Venezian 21, 20133 Milan, Italy. luisella.verotta@unimi.it
Appendino
Giovanni
G
Bombardelli
Ezio
E
Brun
Reto
R
D000818:Animals; D000962:Antimalarials; D001643:Bridged Bicyclo Compounds / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D032446:Myoblasts / Q000187:drug effects; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects*; D051381:Rats; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000737:chemistry / Q000494:pharmacology*
D000962:Antimalarials; D001643:Bridged Bicyclo Compounds; D013729:Terpenes; D010696:Phloroglucinol; C001654:hyperforin