141233-06-9Relevant articles and documents
Inhibition of Trypanosoma cruzi epimastigotes in vitro by iron chelating agents
Jones, Mark M.,Singh, Pramod K.,Lane, Joshua E.,Rodrigues, Rodrigo R.,Nesset, Anna,Suarez, Cristina C.,Bogitsh, Burton J.,Carter, Clint E.
, p. 1158 - 1162 (2007/10/03)
The relative effectiveness of 20 iron chelating agents in suppressing the growth and multiplication of Trypanosoma cruzi epimastigotes has been examined in vitro. 1,2-Dimethyl-3-hydroxypyrid-4-one (L1) and several of its newly synthesized N-substituted analogs containing hydrophobic substituents were significantly more effective than deferoxamine, even though they possess only two donor sites for iron(III) while deferoxamine has six. Analogs with hydrophilic substituents were uniformly less active than L1 itself. Variations in effectiveness as the polarity of the compounds is varied indicate that the ability to cross the cellular membrane is of critical importance in the determination of the in vitro trypanocidal activity of iron(III) chelating agents. A group of four tris(2-aminoethyl)amine based tris-imines were also screened, all of which had poor activity (0-28% inhibition). Among the other iron(III) chelating agents which showed a relatively high level of activity at 50 and 100 μg/ml were salicylhydroxamic acid (70 and 73% inhibition) and hydroxyurea (42 and 52% inhibition). N,N'-Di(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid and acetohydroxamic acid exhibited only slight activity at 50 and 100 μg/ml. The best of these iron(III) chelating agents were as effective against the epimastigote form at both 50 and 100 μg/ml (74-82% inhibition) as benznidazole (81% inhibition), the drug currently used in the clinic.
