Amidoximes of pentamidine: synthesis, trypanocidal and leishmanicidal activity

For the study of the biotransformation of pentamidine and the evaluation of its trypanocidal and leishmanicidal properties the N-hydroxylated derivatives II and III were prepared. In II and III, one or both the terminal amidine moieties of pentamidine are replaced by an amidoxime. These amidoximes II and III were tested against various Trypanosoma species and Leishmania donovani in mice and golden hamsters, respectively. The studies demonstrate that the pentamidine derivatives II and III were active against various trypanosomes (T. brucei; T. vivax; T. congolense). However, besides having a pronounced activity against Trypanosoma rhodesiense compounds II and III exhibit a less action on other Trypanosomes than the standard drugs diminazene and in some cases the parent compound pentamidine. Derivatives II and III were also distinctly active against Leishmania donovani but their leishmanicidal effect was slightly less marked than that of pentamidine.