title: Effects of HIV aspartyl-proteinase inhibitors on Leishmania sp.
abstract: In this work, we have found an antiproliferative effect on Leishmania sp. promastigotes and axenic amastigotes by the human immunodeficiency virus (HIV) aspartyl-proteinase inhibitors, Ac-Leu-Val-Phenylalaninal, Saquinavir mesylate and Nelfinavir, the latter two being used as part of antiretroviral therapy. This effect appears to be the result of cell division blockage. In addition, these drugs induced in culture a decrease in the percentage of co-infected HIV/Leishmania monocytes and amastigotes of Leishmania per macrophage. The finding of a dose-dependent inhibition of Leishmania promastigotes aspartyl-proteinase activity by these drugs allows us to propose this activity as the drug parasite target. A direct action of these HIV aspartyl-proteinase inhibitors on the parasite, would be correlated with the effect that highly active antiretroviral therapy have had in the decrease of HIV/Leishmania coinfection, opening an interesting perspective for new drugs research development based on this novel parasite proteinase family.
authors.affiliation: Laboratorio de Biología Celular de Parásitos, Instituto de Biología Experimental, Universidad Central de Venezuela, Caracas, Venezuela. elizabeth.valdivieso@ciens.ucv.ve
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Valdivieso
authors.forename: Ariadne
authors.initials: A
authors.lastname: Rangel
authors.forename: Javier
authors.initials: J
authors.lastname: Moreno
authors.forename: Jose María
authors.initials: JM
authors.lastname: Saugar
authors.forename: Carmen
authors.initials: C
authors.lastname: Cañavate
authors.forename: Jorge
authors.initials: J
authors.lastname: Alvar
authors.forename: Francehuli
authors.initials: F
authors.lastname: Dagger
mesh_terms: D000818:Animals; D057055:Aspartic Acid Proteases / Q000037:antagonists & inhibitors*; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D018314:Leishmania infantum / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D007894:Leishmania mexicana / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D007896:Leishmaniasis / Q000150:complications / Q000188:drug therapy; D008264:Macrophages / Q000469:parasitology; D051379:Mice; D009000:Monocytes / Q000469:parasitology; D019888:Nelfinavir / Q000494:pharmacology; D019258:Saquinavir / Q000494:pharmacology
chemical_list: D017320:HIV Protease Inhibitors; D057055:Aspartic Acid Proteases; D019888:Nelfinavir; D019258:Saquinavir