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-triaza-cyclonane (TAT). BAT-TE at 270 mu M completely arrested the growth of trypomastigote forms in mouse blood stor ed at 4 degrees C for 24 h (IC50 67.7 +/- 7 mu M), while BAT-TM arrested gr owth at 630 mu M (IC50 158 +/- 17 mu M) and TAT at concentrations >800 mu M (IC50 415 +/- 55 mu M). In T. cruzi-infected mice, BAT-TE and BAT-TM had n o 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 IC50 of 52 +/- 7 mu M against the epimast igote forms while BAT-TM and BAT-TE were inhibitory only at concentrations >250 mu M. The trypanocidal activity of BAT derivatives in blood stored at 4 degrees C makes these compounds potential candidates for the purpose of c learing donated blood of trypomastigotes. (C) 2000 Academic Press.