Anti-Plasmodium activity of imidazole-dioxolane compounds.
A series of imidazole-dioxolane compounds, which we hypothesize should bind to heme and thus interfere with heme catabolism in the parasite, were assayed for inhibitory activity in Plasmodium falciparum cultures and the results were compared to those obtained with Chinese hamster ovary (CHO) cells. The majority of the compounds displayed a similar ratio of inhibitory activity in the two culture systems; however, a number of the compounds tested showed promising anti-Plasmodium activity. The mechanism of action of these compounds remains unclear, however their inability to act synergistically with chloroquine suggests that, if they are inhibiting heme detoxification, they do so in a manner that does not complement the action of chloroquine.
Vlahakis
Jason Z
JZ
Department of Chemistry, Queen's University, Kingston, Ont., Canada K7L 3N6.
Kinobe
Robert T
RT
Nakatsu
Kanji
K
Szarek
Walter A
WA
Crandall
Ian E
IE
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016466:CHO Cells / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D004148:Dioxolanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006418:Heme / Q000737:chemistry / Q000378:metabolism; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008968:Molecular Conformation; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D013237:Stereoisomerism
D000962:Antimalarials; D004148:Dioxolanes; D007093:Imidazoles; D006418:Heme; C010962:formal glycol