In vitro and in vivo studies of trypanocidal activity of dietary isothiocyanates.
Six dietary isothiocyanates, allyl-isothiocyanate, benzyl-isothiocyanate, phenylethyl-isothiocyanate, sulforaphane, erucin, and iberin, were tested for their trypanocidal activities in vitro using culture-adapted bloodstream forms of Trypanosoma brucei. All isothiocyanates showed a dose-dependent effect on the growth of trypanosomes. Five compounds displayed MIC values of 10 µM and GI50 values of around 1.5 µM, while allyl-isothiocyanate exhibited values of 100 and 11 µM, respectively. The compounds showed similar cytotoxic activities against human HL-60 cells with GI50 values of 1-4 µM and MIC values of 10-100 µM. Short-term experiments revealed that, with the exception of allyl-isothiocyanate, isothiocyanates at a concentration of 10 µM kill trypanosomes within 1-4 h of incubation. In contrast, HL-60 cells were not affected by any of the compounds in short-term incubation experiments. Sulforaphane, the most intensively studied isothiocyanate, was also investigated for its in vivo trypanocidal activity. However, administration of 50 mg/kg sulforaphane orally or intraperitoneally for four days had no effect on the parasitaemia in mice infected with T. brucei compared to control animals treated with vehicle alone.
BioMedical Research Centre, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
Dietmar
D
Steverding
BioMedical Research Centre, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
Sarah
S
Michaels
Drug Discovery Unit, Division of Biological Chemistry & Drug Discovery, College of Life Sciences, University of Dundee, Dundee, United Kingdom.
Kevin D
KD
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D000818:Animals; D018922:HL-60 Cells; D006801:Humans; D017879:Isothiocyanates / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects*
D017879:Isothiocyanates; D014344:Trypanocidal Agents