In vitro antiplasmodial activity of prenylated chalcone derivatives of hops (Humulus lupulus) and their interaction with haemin.
OBJECTIVE
There is an urgent need to discover new antimalarials, due to the spread of chloroquine resistance and the limited number of available drugs. Chalcones are one of the classes of natural products that are known to possess antiplasmodial properties. Therefore, the in vitro antiplasmodial activity of the main hop chalcone xanthohumol and seven derivatives was evaluated. In addition, the influence of the compounds on glutathione (GSH)-dependent haemin degradation was analysed to determine its contribution to the antimalarial effect of chalcones.


METHODS
In vitro antiplasmodial activity was evaluated against the chloroquine-sensitive strain poW and the multiresistant clone Dd2 using a [(3)H]hypoxanthine-incorporation assay. Inhibition of GSH-dependent haemin degradation was analysed by a multiwell plate assay at 11 microM.


RESULTS
Of the eight compounds tested, four possessed activity with IC(50) values<25 microM against at least one of the two strains of Plasmodium falciparum. The main hop chalcone, xanthohumol, was most active with IC(50) values of 8.2+/-0.3 (poW) and 24.0 +/- 0.8 microM (Dd2). Three of these compounds were additionally active in the haemin-degradation assay.


CONCLUSIONS
The results demonstrate for the first time the ability of chalcone derivatives to interfere with the haemin-degradation process of P. falciparum. This effect might contribute to their antiplasmodial activity. Nevertheless, as one compound showed inhibition of P. falciparum without being able to interact with GSH-dependent haemin degradation, other modes of action must add to the observed antiparasitic activity of hop chalcones.
Frölich
Sonja
S
Institut für Pharmazie (Pharmazeutische Biologie), Freie Universität Berlin, Königin-Luise-Str. 2-4, D-14195 Berlin, Germany.
Schubert
Carola
C
Bienzle
Ulrich
U
Jenett-Siems
Kristina
K
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D047188:Chalcones / Q000494:pharmacology*; D006427:Hemin / Q000378:metabolism*; D027582:Humulus / Q000737:chemistry*; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000378:metabolism; D017368:Protein Prenylation
D000962:Antimalarials; D047188:Chalcones; D006427:Hemin