Antileishmanial activity of HIV protease inhibitors.
The proteasomes of some protozoa are possible targets for chemotherapy. Leishmaniasis is a major health problem in human immunodeficiency virus (HIV) co-infected subjects. Two HIV protease inhibitors (PI), indinavir and saquinavir, have been shown to block proteasome functions; we therefore investigated their effects on the growth of two Leishmania spp. (Leishmania major and Leishmania infantum). After 24 h of treatment, both drugs exhibited a dose-dependent antileishmanial activity, with 50% lethal dose (LD50) values of, respectively, 8.3 microM and 7 microM on L. major; minor activity was observed on L. infantum. These results add new in vitro insights into the wide-spectrum efficacy of PI and suggest studying their action on amastigote forms of leishmania within macrophages in order to validate their potential contribution against opportunistic infections in treated seropositive patients.
Savoia
Dianella
D
Laboratory of Microbiology, Department of Clinical and Biological Sciences, University of Torino at S. Luigi Gonzaga Hospital, 10043 Orbassano, Torino, Italy. dianella.savoia@unito.it
Allice
Tiziano
T
Tovo
Pier-Angelo
PA
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D019469:Indinavir / Q000494:pharmacology*; D018314:Leishmania infantum / Q000187:drug effects*; D018320:Leishmania major / Q000187:drug effects*; D007928:Lethal Dose 50; D019258:Saquinavir / Q000494:pharmacology*
D000981:Antiprotozoal Agents; D017320:HIV Protease Inhibitors; D019469:Indinavir; D019258:Saquinavir