Amidine derivatives and Leishmania amazonensis: an evaluation of the effect of nitric oxide (NO) production on the parasite-macrophage interaction.
Previous work has demonstrated that N-N'-diphenyl-R-benzamidine was highly effective against Leishmania amazonensis promastigotes/axenic amastigotes and Trypanosoma evansi trypomastigotes and the compound with a methoxy substituent, was the most effective derivative in the parasite-macrophage interaction. Comparative analysis of the nitric oxide (NO) released from the culture infection's supernatant showed the amidine to be less effective than pentamidine Isethionate as a reference drug. Additionally, in order to verify if the methoxylated derivative interferes with NO production by L. amazonensis, the effect of the amidine on the constitutive nitric oxide synthase (cNOS) purified from parasites, was examined, but demonstrated less activity in comparison with the reference drug. This data contributes to studies concerning the metabolic targets present in Leishmania parasites for leishmanicidal drugs.
Temporal
R M
RM
Department of Immunology, Instituto Oswaldo Cruz/FIOCRUZ, Rio de Janeiro, Brazil. temporal@ioc.fiocruz.br
Cysne-Finkelstein
L
L
Echevarria
A
A
Silva-Gonçalves
A J
AJ
Leon
L L
LL
Genestra
M S
MS
D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D007891:Leishmania / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D007896:Leishmaniasis / Q000188:drug therapy / Q000469:parasitology; D008264:Macrophages / Q000201:enzymology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D010419:Pentamidine / Q000494:pharmacology
D000578:Amidines; D009569:Nitric Oxide; D010419:Pentamidine; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III