Quassinoids exhibit greater selectivity against Plasmodium falciparum than against Entamoeba histolytica, Giardia intestinalis or Toxoplasma gondii in vitro.
The in vitro activities of a series of quassinoids against Plasmodium falciparum, Entamoeba histolytica, Giardia intestinalis and Toxoplasma gondii have been compared with their in vitro cytotoxic effects against KB cells (human epidermoid carcinoma of the nasopharynx). All of the compounds tested were more toxic to KB cells than to G. intestinalis, but four (ailanthinone, bruceine D, brusatol and glaucarubinone) were slightly less toxic to KB cells than to E. histolytica. Glaucarubinone was similarly more toxic to intracellular T. gondii than to KB cells but ailanthinone was more selective (36 times more toxic to T. gondii than to KB cells). All of the compounds were more toxic to P. falciparum than to KB cells; the most selective quassinoids--glaucarubinone, bruceine D, ailanthinone and brusatol--were found to have toxicity/activity ratios of 285, 76, 48 and 32 respectively. These results suggest that quassinoids have a selective action on P. falciparum. Further studies to elucidate the basis for this are in progress.
Department of Pharmacognosy, School of Pharmacy, University of London, United Kingdom.
C W
CW
Wright
M M
MM
Anderson
D
D
Allen
J D
JD
Phillipson
G C
GC
Kirby
D C
DC
Warhurst
H R
HR
Chang
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D004748:Entamoeba histolytica / Q000187:drug effects*; D016829:Giardia lamblia / Q000187:drug effects*; D005900:Glaucarubin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects*; D014122:Toxoplasma / Q000187:drug effects*; D014315:Triterpenes / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000981:Antiprotozoal Agents; D014315:Triterpenes; D005900:Glaucarubin