Proteinase inhibitors as antileishmanial agents

Leishmania mexicana mexicana amastigote proteinase activity was largely inhibited by low concentrations of leupeptin, antipain and two epoxysuccinates, compounds known to affect cysteine proteinases. Of these inhibitors, only two had leishmanicidal activity. trans-Dicyclohexylepoxysuccinate at 10 microgram/ml inhibited the in vitro transformation of L. m. mexicana amastigotes to promastigotes by greater than 50%. Antipain was a potent antileishmanial agent, which inhibited promastigote growth over seven days by 50% at 0 . 5 microgram/ml. The number of amastigotes that transformed in vitro to promastigotes was reduced 78% by antipain at 0 . 1 microgram/ml. Each of the three diamidines investigated (pentamidine isothionate, amicarbilide and M and B 4596) exhibited marked antileishmanial activity, but only M and B 4596 had any significant effect (36% inhibition at 33 microgram/ml) on L. m. mexicana amastigote proteinase activity.