The recent report on N,N'-bis(4-amidinophenyl)piperazine (Figure 16) , which was shown to be very effective in vivo anti-trypanosomal agent has attracted the interest in this compound [56] . Hence in search for new HAT chemotherapy Dardonville C et al [57] decided to carry out an in vitro screening of a total of 62 compounds against the parasite T. brucei rhodesiense taken from their in-house library. Based on this they showed that bisguanidine and especially bis(2-aminoimidazoline)diphenyl compounds displayed potent anti-trypanosomal activity in vitro and vivo against T. b. rhodesiense, the causative agent of acute HAT [58, 59] . Among the 62 compounds screened, compounds1c, 28b, 32b and 41b ( Figure 17 ) showed excellent in vitro activity (49nM, 69 nM, 22 nM and 118 nM respectively) as well as high selectivity (>5294, 3072, 29.5 and 881respectively) for the parasite. These studies revealed that compounds bearing 2-aminoimidazoline cations had higher selectivity for the parasite and similar activities with respect to their guanidine counterparts. In addition, a correlation between anti-trypanosomal activity and DNA binding affinity was observed, suggesting a possible mechanism of action for these compounds. Those molecules that showed an excellent in vitro activity as well as high selectivity for the parasite represent new anti-trypanosomal lead compounds. Fig. 16. N,N'-bis(4-amidinophenyl) piperazine