INHIBITION BY DICATIONS OF IN VITRO GROWTH OF LEISHMANIA MAJOR AND LEISHMANIA TROPICA: CAUSATIVE AGE
June 27th, 2008 | by admin |INHIBITION BY DICATIONS OF IN VITRO GROWTH OF LEISHMANIA MAJOR AND LEISHMANIA TROPICA: CAUSATIVE AGENTS OF OLD WORLD CUTANEOUS LEISHMANIASIS.
Old World cutaneous leishmaniasis is caused by infection with Leishmania major and L. tropica. Pentamidine and related dications exhibit broad spectrum antiprotozoal activity. Based on the previously reported efficacy of these compounds against related organisms, eighteen structural analogs of pentamidine were evaluated for in vitro antileishmanial activity, using pentamidine as the standard reference drug for comparison. Furan analogs and reversed amidine compounds were examined for activity against L. major and L. tropica promastigotes. The most active compounds against both Leishmania spp. were in the reversed amidine series. DB 745 and DB 746 exhibited the highest activity against L. major and DB 745 was the most active compound against L. tropica. Both of these compounds exhibited 50% inhibitory concentrations (IC50) below one nanomolar for L. major. Ten reversed amidines were also tested for their ability to inhibit growth in an axenic amastigote model. Nine of ten reversed amidine analogs were active at concentrations below one micromolar. These results justify further study of dicationic compounds as potential new agents for treating cutaneous leishmaniasis.
Rosypal A, Werbovetz K, Salem M, Stephens C, Kumar A, Boykin D, Hall J, Tidwell R.