The experimental chemotherapy of leishmaniasis, III Detection of antileishmanial activity in some new synthetic compounds in a tissue culture model

Abstract

Using a tissue culture system described earlier, the leishmanicidal action of over 100 compounds was examined against amastigotes of Leishmania mexicana, L. tropica and L. donovani. In most cases this was only determined against 1 of these species. Good activity was found in a variety of chemical structures many of which are also known to have antimalarial effects. Some of the active compounds act as inhibitors of dihydrofolate reductase, mitochondrial respiration or other metabolic systems in Plasmodium infections. The present findings may give some indication of the existence of such systems in parasites of the genus Leishmania. Among the more active compounds with the best therapeutic indices were several amidineureas, 8-aminoquinolines, quinine analogues, quinolinemethanols, quinazolines, triazines and thiazoles, as well as a variety of miscellaneous structures. One of the most active was a thiophene derivative. The relevance of these data to the evaluation of new compounds as potential leishmanicides for clinical study is discussed. Stress is laid on the need to follow up the present observations in animal models.