2-Amino diphenylsulfides as new inhibitors of trypanothione reductase

Trypanothione reductase (TR) is the primary enzyme responsible for the reduction of trypanothione, the analog of glutathione found in trypanosomatidae. We have discovered a series of diphenylsulfides which are potent inhibitors of TR and have no activity on mammalian glutathione reductase. These compounds are also active in vitro on various stages of the parasite. Although structurally related to phenothiazines, which are known to be TR inhibitors, these compounds are devoided of any neuroleptic activity, making them attractive leads to develop specific and non toxic anti-chagasic drugs.