Novel alkylpolyaminoguanidines and alkylpolyaminobiguanides with potent antitrypanosomal activity

A series of polyaminoguanidines and polyaminobiguanides were synthesized and evaluated as potential antitrypanosomal agents. These analogues inhibit trypanothione reductase (TR) with IC50 values as low as 0.95 μM, but do not inhibit the closely related human enzyme glutathione reductase (GR). The most effective analogues, 7a, 7b and 8d, inhibited parasitic growth in vitro with IC50 values of 0.18, 0.09 and 0.18 μM, respectively. These agents represent a promising new class of potential antitrypanosomal agents.

The synthesis and antitrypanosomal activity of analogues related to 7b (IC50 = 0.09 μM) and 8d (IC50 = 0.18 μM) are described.Figure optionsDownload as PowerPoint slide