Premium
Assessment of Leishmanicidal and Trypanocidal Activities of Aliphatic Diamine Derivatives
Author(s) -
Yamanaka Celi.,
Giordani Raquel B.,
Rezende Celso O.,
Eger Iriane,
Kessler Rafael L.,
Tonini Maiko L.,
Moraes Milene H.,
Araújo Debora P.,
Zuanazzi Jose A.,
Almeida Mauro V.,
Steindel Mario
Publication year - 2013
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12191
Subject(s) - benznidazole , amastigote , trypanosoma cruzi , chagas disease , leishmania braziliensis , in vitro , mechanism of action , stereochemistry , depolarization , chemistry , pharmacology , biology , biochemistry , leishmania , leishmaniasis , immunology , biophysics , parasite hosting , cutaneous leishmaniasis , world wide web , computer science
Leishmanicidal and trypanocidal activity of seventeen lipophilic diamines was evaluated in vitro against L eishmania braziliensis , L . chagasi , and T rypanosoma cruzi . Twelve compounds presented anti‐ L eishmania and six showed anti‐ T . cruzi amastigote activity. Compound 14 ( N ‐tetradecyl‐1,4‐butanediamine) was the most active against both L . braziliensis (IC 50 = 2.6 μ m ) and L . chagasi (IC 50 = 3.0 μ m ) which showed a selectivity index ( SI ) >100. N ‐decyl‐1,6‐hexanediamine (compound 9 ) presented an IC 50 = 1.6 μ m and SI >187 and was over six times more potent than the reference drug benznidazole against T . cruzi . Treatment of infected or uninfected macrophages with compounds 9 and 14 did not induce significant TNF α and NO production. Four compounds ( 15 , 16 , 22 , and 23 ) inhibited 78.9%, 77.7%, 83.7%, and 70.1% of r TRL b activity, respectively, and compound 23 inhibited 73.3% of rTRT c activity at 100 μ m . A concentration‐dependent effect on mitochondrial membrane depolarization was observed in T . cruzi epimastigotes treated with compound 9 , suggesting this mechanism may be involved in the trypanocidal effect. On the contrary, in L . braziliensis promastigotes treated with compound 14 , no mitochondrial depolarization was observed. Our results demonstrate that N ‐decyl‐1,6‐hexanediamine and N ‐tetradecyl‐1,4‐butanediamine are promising molecules for the development of novel leading compounds against T . cruzi and Leishmania spp., particularly given a possible alternative mechanism of action.