Aminothiol multidentate chelators against Chagas disease.
Three compounds of an aminothiol family of iron chelators were examined for activity against trypomastigote (human) and epimastigote (vector) forms of Trypanosoma cruzi: tetraethyl and tetramethyl derivatives of ethane-1,2-bis (N-1-amino-3-ethyl butyl-3-thiol) (BAT-TE and BAT-TM) and N',N',N'-tris-(2-methyl-2-mercaptopriopyl)- 1,4,7-triazacyclonane (TAT). BAT-TE at 270 microM completely arrested the growth of trypomastigote forms in mouse blood stored at 4 degrees C for 24 h (IC(50) 67.7+/-7 microM), while BAT-TM arrested growth at 630 microM (IC(50) 158+/-17 microM) and TAT at concentrations >800 microM (IC(50) 415+/-55 microM). In T. cruzi-infected mice, BAT-TE and BAT-TM had no anti-trypanosomal activity in doses up to 200 mg/kg, whether the route of administration was intraperitoneal or oral, and TAT was not tested due to insufficient quantity. TAT had an IC(50) of 52+/-7 microM against the epimastigote forms while BAT-TM and BAT-TE were inhibitory only at concentrations >250 microM. The trypanocidal activity of BAT derivatives in blood stored at 4 degrees C makes these compounds potential candidates for the purpose of clearing donated blood of trypomastigotes.
Deharo
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E
Institut de Recherche pour le Développement (IRD), La Paz, CP 9214, Bolivia. plantibba@megalink.com
Loyevsky
M
M
John
C
C
Balanza
E
E
Ruiz
G
G
Muñoz
V
V
Gordeuk
V R
VR
D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy*; D004195:Disease Models, Animal; D007502:Iron Chelating Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008024:Ligands; D051379:Mice; D018512:Parasitemia / Q000188:drug therapy / Q000469:parasitology; D013438:Sulfhydryl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D014349:Trypanosoma cruzi / Q000187:drug effects
D007502:Iron Chelating Agents; D008024:Ligands; D013438:Sulfhydryl Compounds