In addition to above mentioned prodrug synthesis Boykin DW et al [86] also reported that bis-amidoximes and bis-O-alkylamidoximes of a number of diamidine systems are effective prodrugs. In order to develop orally effective anti-trypanosomal agents, they synthesized these two types of potential prodrugs in the terphenyl series. It was found that compound 10b and 10d ( Figure 32 ) showed good activity in the range of 2 nM. Among these compounds 10b had lower cytotoxicity (6.4μM) profile but had very poor in vivo activity (cured none of the infected animal in STIB900 mouse model). Whereas compound 10d showed excellent in vivo activity, by curing all the infected animals upon oral administration in STIB900 mouse model. To capitalize on the efficacy of these potent dications, other prodrugs that rely on different bioconversion pathways need to be developed. 