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 μM completely arrested the growth of trypomastigote forms in mouse blood stored at 4°C for 24 h (IC₅₀ 67.7 ± 7 μM), while BAT-TM arrested growth at 630 μM (IC₅₀ 158 ± 17 μM) and TAT at concentrations >800 μM (IC₅₀ 415 ± 55 μM). In T. cruzi-infected mice, BAT-TE and BAT-TM had no antitrypanosomal 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 μM against the epimastigote forms while BAT-TM and BAT-TE were inhibitory only at concentrations >250 μM. The trypanocidal activity of BAT derivatives in blood stored at 4°C makes these compounds potential candidates for the purpose of clearing donated blood of trypomastigotes. (C) 2000 Academic Press.