Leishmania mexicana: drug sensitivities of promastigotes and transforming amastigotes.

A comparison has been made of the effects of a range of antiprotozoal drugs and other metabolic inhibitors upon growing promastigotes and transforming amastigotes of Leishmania mexicana mexicana. Amastigotes transforming to promastigotes in vitro were highly susceptible to 2-mercaptoacetate, 4-pentenoate, alpha-difluoromethylornithine, ethidium bromide, acridine orange, pentamidine isethionate, allopurinol, amphotericin B, menoctone and pentostam. Promastigotes were in most cases less sensitive to these inhibitors. The results reiterate that the biochemical differences between the two developmental forms are reflected in their sensitivities to inhibitors. The transformation in vitro of Leishmania amastigotes to promastigotes may be a useful model for use as a primary screen for antileishmanial agents.

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.