Aminothiol multidentate chelators against Chagas disease

Abstract

Abstract 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 4º C for 24 h (IC(50) 67.7+/-7 µM), while BAT-TM arrested growth at 630 µM (IC(50) 158+/-17 µM) and TAT at concentrations >800 µM (IC(50) 415+/-55 µM). 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 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 4º C makes these compounds potential candidates for the purpose of clearing donated blood of trypomastigotes.